BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

OBJECTIVE: The purpose of this study is to determine the dose reduction of different shielding materials at various distances from a 177Lu photon radiation source. METHODS: Two protective aprons with lead equivalent thicknesses of 0.25 mm and 0.35 mm and tungsten-containing rubber (TCR) were used as shielding materials. A vial containing 177Lu was sealed in a lead container so that a narrow beam went out through a 3 mm-diameter hole. The dose rate was measured at distances of 0, 10, 50, 100, and 200 cm from the source using a NaI scintillation survey meter to obtain the rate of dose reduction. TCR was tested with thicknesses ranging from 0.3 to 1.0 mm at 0.1 mm intervals and from 1.0 to 4.0 mm at 0.5 mm intervals. RESULTS: At distances of 0, 10, 50, 100, and 200 cm, the dose reduction for the lead equivalent thickness of 0.25 mm were 32.7%, 54.5%, 93.1%, 97.9%, and 99.6%, respectively; and for the lead equivalent thickness of 0.35 mm were 53.4%, 70.6%, 95.6%, 98.9%, and 99.6%, respectively. Without any shielding, the dose rate decreased by 34.4% at 10 cm and by 88.8% at 50 cm from the radiation source. The dose reduction for the TCR thickness of 3.5 mm was 89.8% at 0 cm and 93.3% at 10 cm. The TCR thickness of 0.4 mm provided a dose reduction comparable to or greater than that of the 0.25 mm lead equivalent, whereas the TCR thickness of 1.0 mm or greater provided a dose reduction comparable to that of the 0.35 mm lead equivalent. CONCLUSIONS: Achieving a reduction of 95% or more requires the 0.25 mm lead equivalent for a distance of 100 cm, the 0.35 mm lead equivalent for 50 cm, the TCR thickness of 0.3 mm for 100 cm, or the TCR thickness of 0.9 mm for 50 cm. Without wearing a protective apron, a reduction of approximately 95% is observed at distances greater than 100 cm. These findings would be useful for medical staff engaging in related activities.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan–Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32–8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43–3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35–3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

This study aimed to examine occupational radiation exposure to the lens of the eyes during endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, prospective, observational cohort study, we collected data regarding occupational radiation exposure to the lens of the eyes during ERCP. We measured radiation exposure of patients and examined its correlation with occupational exposure. In dosimetrically-measured ERCPs (n = 631), the median air kerma at the patient entrance reference point, air kerma-area product, and fluoroscopy time were 49.6 mGy, 13.5 Gycm2, and 10.9 min, respectively. The median estimated annual radiation dose to the lens of the eyes was 3.7, 2.2, and 2.4 mSv for operators, assistants, and nurses, respectively. Glass badge over lead aprons and eye dosimeter results were similar in operators but differed in assistants and nurses. A strong correlation was shown between eye dosimeter measurements and patients' radiation exposure. The shielding rates of the lead glasses were 44.6%, 66.3%, and 51.7% for operators, assistants, and nurses, respectively. This study revealed the actual occupational exposure dose for the lens of the eyes during ERCP and the efficacy of lead glass. Values of radiation exposure to patients can help estimate exposure to the lens of the eyes of medical staff.

OBJECTIVES: We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy-fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow-up survey of doctors, nurses, and technologists in Japan. METHODS: We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy-fluoroscopy departments. The questionnaire included 17 multiple-choice questions divided into three parts: background, equipment, and knowledge. RESULTS: We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy-six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5-year lens REX limit (56%). CONCLUSIONS: There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments.

BACKGROUND/AIM: This study evaluated the impact of knowledge-based plan (KBP) model improvement on plan complexity and delivery accuracy in volumetric modulated arc therapy (VMAT) for prostate cancer at multiple institutions. MATERIALS AND METHODS: Five institutions created the first KBP model before April 2017 and subsequently devised a new model (second model) based on feedback from the first KBP and the efforts of planners after April 2019. The dose-volume histogram (DVH) parameters were validated for two prostate cancer cases between the first and second KBPs. Plan complexity metrics, of the modulation complexity score for VMAT (MCSv), closed leaf score (CLS), small aperture score (SAS), and leaf travel (LT), were compared. The delivery accuracy metrics of γ pass rate and point dose discrepancy (plan vs. measurement) at isocenter were also compared. RESULTS: There were no significant differences in DVH parameters between the KBPs. Conversely, V50% of the rectum and bladder was reduced in 6/10 and 8/10 patients, respectively, and these variations were also converged from the first KBP to the second KBP. The mean±1SDs of MCSv, CLS, SAS20mm, and LT (first KBP vs. second KBP) were 0.27±0.033 vs. 0.26±0.044, 0.062±0.032 vs. 0.14±0.091, 0.59±0.048 vs. 0.70±0.14, and 411.91±32.08 mm vs. 548.33±127.50 mm, respectively. The delivery accuracy did not differ, whereas MCSv was moderately correlated with the point dose discrepancy. CONCLUSION: Multi-leaf collimator motion could be more complex with KBP model improvement, which had the potential to deteriorate the delivery accuracy.

Abstract In this manuscript, we present the guideline for use of meta-[²¹¹At] astatobenzylguanidine ([²¹¹At] MABG), a newly introduced alpha emitting radiopharmaceutical to the up-coming World’s first clinical trial for targeted alpha therapy (TAT) at Fukushima Medical University in Japan, focusing on radiation safety issues in Japan. This guideline was prepared based on a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on Oct. 5th, 2021. The study showed that patients receiving [²¹¹At] MABG do not need to be admitted to a radiotherapy room and that TAT using [²¹¹At] MABG is possible on an outpatient basis. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers or patient’s family members. In this guideline, the following contents are also included: precautions for patients and their families, safety management associated with the use of [²¹¹At] MABG, education and training, and disposal of medical radioactive contaminants. TAT using [²¹¹At] MABG in Japan should be carried out according to this guideline. Although this guideline is based on the medical environment and laws and regulations in Japan, the issues for radiation protection and evaluation methodology presented in this guideline are useful and internationally acceptable as well.

Fluoroscopy-guided endoscopic procedures (FGEPs) are rapidly gaining popularity in the field of gastroenterology. Radiation is a well-known health hazard. Gastroenterologists who perform FGEPs are required to protect themselves, patients, as well as nurses and radiologists engaged in examinations from radiation exposure. To achieve this, all gastroenterologists must first understand and adhere to the International Commission on Radiological Protection Publication. In particular, it is necessary to understand the three principles of radiation protection (Justification, Optimization, and Dose Limits), the As Low As Reasonably Achievable principle, and the Diagnostic Reference Levels (DRLs) according to them. This review will mainly explain the three principles of radiation exposure protection, DRLs, and occupational radiological protection in interventional procedures while introducing related findings. Gastroenterologists must gain knowledge of radiation exposure protection and keep it updated.

BACKGROUND: The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of 177 Lu-DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs). METHODS: From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients. RESULTS: The mean absorbed doses of 177 Lu-DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%-76%). ORRs of the midgut and non-midgut NETs were 60% (90% CI, 19%-92%) and 50% (90% CI, 22%-78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non-midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%-91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%). CONCLUSION: 177 Lu-DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs.

Fluoroscopy forms an essential part of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) and hepaticogastrostomy with antegrade stenting (EUS-HGAS). To date, no study has assessed and compared radiation exposure between EUS-HGS and EUS-HGAS. This study aimed to compare the radiation exposure parameters between EUS-HGS and EUS-HGAS. This retrospective single-center cohort study included consecutive patients who underwent EUS-HGS or EUS-HGAS from October 2017 to March 2019. The air kerma (AK: mGy), kerma-area product (KAP: Gycm2), fluoroscopy time (FT: min), and procedure time (PT: min) were assessed and compared between the two procedures. Altogether, 45 and 24 patients underwent EUS-HGS and EUS-HGAS, respectively. The median AK, KAP, FT, and PT were higher in the EUS-HGAS group than in the EUS-HGS group. A comparison revealed no difference in the technical success rate, complications rate, adverse event occurrence rate, and re-intervention rate between both procedures. This is the first report in which radiation exposure was used as a comparative parameter between EUS-HGS and EUS-HGAS. This study revealed that radiation exposure is significantly higher in EUS-HGAS than in EUS-HGS. Increased awareness on radiation exposure is warranted among gastroenterologists so that they choose the procedure with lower radiation exposure in cases where both procedures are indicated.

BACKGROUND: Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan. METHODS: This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (Ka,r: mGy), air kerma area product (PKA: Gycm2), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525). FINDINGS: Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of Ka,r (mGy), PKA (Gycm2), and FT (min) were 69/145 mGy, 16/32 Gycm2, and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm2 and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm2 and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm2, and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm2 and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely. INTERPRETATION: This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values. FUNDING: This work was supported by a clinical research grant from the Japanese Society of Gastroenterology.

OBJECTIVES: The transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP-D) cannot be performed without fluoroscopy, and there are many situations in which fluoroscopy is required even in endoscopic ultrasound-guided drainage (EUS-D). Previous studies have compared the efficacy, but not the radiation exposure of EUS-D and ERCP-D. While radiation exposure in ERCP-D has been previously evaluated, there is a paucity of information regarding radiation doses in EUS-D. This study aimed to assess radiation exposure in EUS-D compared with that in ERCP-D. METHODS: This retrospective single-center cohort study included consecutive patients who underwent EUS-D and ERCP-D between October 2017 and March 2019. The air kerma (AK, mGy), kerma-area product (KAP, Gycm2 ), fluoroscopy time (FT, min), and procedure time (PT, min) were assessed. The invasive probability weighting method was used to qualify the comparisons. RESULTS: We enrolled 372 and 105 patients who underwent ERCP-D and EUS-D, respectively. The mean AK, KAP, and FT in the EUS-D group were higher by 53%, 28%, and 27%, respectively, than those in the ERCP-D group, whereas PT was shorter by approximately 11% (AK, 135.0 vs. 88.4; KAP, 28.1 vs. 21.9; FT, 20.4 vs. 16.0; PT, 38.7 vs. 43.5). The sub-analysis limited to biliary drainage cases showed the same trend (AK, 128.3 vs. 90.9; KAP, 27.0 vs. 22.2; FT, 16.4 vs. 16.1; PT, 32.5 vs. 44.4). CONCLUSIONS: This is the first study to assess radiation exposure in EUS-D compared with that in ERCP-D. Radiation exposure was significantly higher in EUS-D than in ERCP-D, despite the shorter procedure time.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4-109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax < 125 Gy (BED10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax < 125 Gy (BED10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax < 125 Gy (BED10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume.

Although many interventions involving radiation exposure have been replaced to endoscopic procedure in the gastrointestinal and hepatobiliary fields, there remains no alternative for enteroscopy and endoscopic retrograde cholangiopancreatography (ERCP), which requires the use of radiation. In this review, we discuss the radiation doses and protective measures of endoscopic procedures, especially for ERCP. For the patient radiation dose, the average dose area product for diagnostic ERCP was 14-26 Gy.cm², while it increased to as high as 67-89 Gy.cm² for therapeutic ERCP. The corresponding entrance skin doses for diagnostic and therapeutic ERCP were 90 and 250 mGy, respectively. The mean effective doses were 3- 6 mSv for diagnostic ERCP and 12-20 mSv for therapeutic ERCP. For the occupational radiation dose, the typical doses were 94 μGy and 75 μGy for the eye and neck, respectively. However, with an over-couch-type X-ray unit, the eye and neck doses reached as high as 550 and 450 μGy, with maximal doses of up to 2.8 and 2.4 mGy/procedure, respectively.A protective lead shield was effective for an over couch X-ray tube unit. It lowered scattered radiation by up to 89.1% in a phantom study. In actual measurements, the radiation exposure of the endoscopist closest to the unit was reduced to approximately 12%. In conclusion, there is a clear need for raising awareness among medical personnel involved endoscopic procedures to minimise radiation risks to both the patients and staff.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

This paper does not necessarily reflect the views of the International Commission on Radiological Protection.Kawamata Town in Date District, Fukushima Prefecture is located more than 30 km north-west of Fukushima Daiichi nuclear power plant, but on 22 April 2011, part of the Yamakiya District of Kawamata Town was designated as a planned evacuation area. The exposure of children was a concern in Kawamata Town. Based on the proposal of Kindai University, Kawamata Town Board of Education took the initiative to measure individual radiation doses with an integrated dosimeter (glass badge) for all kindergarten children, nursery school children, elementary school students, and junior high school students in the town. These measurements were continued for nearly 3 years from June 2011 until the end of March 2014. The total number of measurements was approximately 16,800 across 11-cycle measurement, with 3 months' accumulation taken as one-cycle measurement. Kindai University provided financial support for the glass badge measurement service, and cooperated in the analysis of measured values and the development of advice based on the results. The main body implementing the measurements was Kawamata Town Board of Education, and the data obtained belong to Kawamata Town. When measurements were starting to be taken, schools got involved in the collection and distribution of dosimeters after explanations were provided to principals and school nurses who were in charge of risk communication. Thanks to the efforts of the schools, the recovery rate exceeded 90%, increasing the reliability of the measurements. It was clear who needed the information - the children and their parents. Kawamata Town Board of Education summarised the cumulative dose results for each measurement and notified parents via personal reports. These were sent to parents with advice on measurement results prepared by Kindai University, and care was taken to ensure that people could understand the measured results. Further briefing sessions were held as appropriate. At the briefing sessions, at the request of Kawamata Town Board of Education, the faculty members of Kindai University explained the measurement results from a professional point of view, and a professor from the Faculty of Medicine provided individual health consultations. Kawamata Town took the lead in using specialists to gain peace of mind, and this was key to the project's success. The situation was managed by taking measurements by dosimetry, and asking experts to interpret the data and provide advice to help reassure the residents. Keywords: Experts; Exposure of children; Glass badges; Nuclear accident; Support for reconstruction.

OBJECTIVES: We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy-fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow-up survey of doctors, nurses, and technologists in Japan. METHODS: We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy-fluoroscopy departments. The questionnaire included 17 multiple-choice questions divided into three parts: background, equipment, and knowledge. RESULTS: We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy-six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5-year lens REX limit (56%). CONCLUSIONS: There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments.

BACKGROUND AND AIMS: It is essential for endoscopists, technologists, and nurses to understand radiation protection. However, protective equipment usage is still low, and there is little awareness of radiation protection in practice. METHODS: We conducted a questionnaire survey on radiation protection from January to February 2020. The participants were medical staff, including medical doctors, nurses, and radiological and endoscopy technician in endoscopy-fluoroscopy departments. The questionnaire included 14 multiple-choice questions divided among three parts: background, equipment, and knowledge. RESULTS: We surveyed a total of 282 subjects from 26 institutions. There were 168 medical doctors (60%), 90 nurses (32%), and 24 technologists (9%). Although almost all staff members (99%) always wore a lead apron, only a few wore a thyroid collar (32%) and lead glasses (21%). The rate of wearing a radiation dosimeter was insufficient (69%), especially among doctors (52%). A few subjects knew the radiation exposure dose of each procedure (15%), and slightly over half had attended lectures on radiation protection (64%) and knew about the three principles of radiation protection (59%). Protection adherence did not differ by years of experience, knowledge of fluoroscopy, awareness of radiation exposure doses, or attendance at basic lectures on radiation protection. However, medical doctors who were aware of the radiation exposure dose of each procedure were significantly more likely to wear dosimeters than those who were not (p = 0.0008). CONCLUSION: Medical staff in endoscopy departments in Japan do not have enough radiation protection equipment or education.

BACKGROUND: Based on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics. METHODS: This non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs). RESULTS: In the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population. CONCLUSION: In a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.

Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name "dedicated breast PET" from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, "breast PET" has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging.

A 73-year-old man with lung cancer underwent bone scintigraphy for disease staging. Diffuse myocardial technetium hydroxymethylene diphosphonate (99mTc-HMDP) uptake was incidentally found. A diagnosis of amyloid transthyretin (ATTR) cardiac amyloidosis was suspected, although the patient had no symptoms at this time. Single-photon emission computed tomography (SPECT) showed particularly strong uptake in the ventricular septum. Cardiac magnetic resonance imaging (CMR) showed widespread subendocardial and partly transmural enhancement of the left ventricular myocardium on delayed postcontrast T1-weighted images. These findings were consistent with ATTR cardiac amyloidosis. 18F-FDG uptake in the left ventricle wall was observed on PET/CT. He was finally diagnosed with ATTR by endomyocardial biopsy. There are two major subtypes of cardiac amyloidosis: ATTR amyloidosis and amyloid light-chain (AL) amyloidosis. Endomyocardial biopsy is the gold standard for diagnosis. Recently, however, several reports have shown that bone scintigraphy using a 99mTc-labelled bone-seeking agent can detect ATTR cardiac amyloidosis and differentiate it from AL amyloidosis. Bone scintigraphy may play an important role in the detection and differentiation of ATTR cardiac amyloidosis.

INTRODUCTION: The global needs for a reduction in radiation exposure (RE) are increasing. Endoscopic retrograde cholangiopancreatography (ERCP) is a significant fluoroscopic procedure in the gastrointestinal field. However, the actual RE in ERCP and its annual trend are still unclear. Therefore, we examined the yearly trend of RE in ERCP. METHODS: This retrospective, single-center cohort study included consecutive cases of ERCP from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm2), and fluoroscopy time (FT, min). We also evaluated the annual trend of the RE before and after the fluoroscopy device update. RESULTS: In total, 2,174 patients receiving ERCP were enrolled. Among these, the mean age was 74.3 years, and 913 patients were women (42.0%). The median/third quartile values of AK (mGy), DAP (Gycm2), and FT (min) were 109/234 mGy, 13.3/25.8 Gycm2, and 18.2/27.7 minutes. The annual AK, DAP, and FT from 2012 to 2019 were 138, 207, 173, 177, 106, 71.0, 45.0, and 33.3 mGy; 23, 21.4, 19, 18.3, 11.9, 9.0, 6.8, and 6.4 Gycm2; and 12.5, 12.1, 9.7, 9.8, 8.2, 10.8, 9.4, and 10.3 minutes, respectively. The corresponding values before and after the update in July 2016 were 177 and 52 mGy (P < 0.0001), 19.2 and 7.6 Gycm2 (P < 0.0001), and 10.2, and 9.9 minutes (P = 0.05), respectively. DISCUSSION: The RE from ERCP tended to decrease every year, especially after fluoroscopy device updates.

Background and study aims  Fluoroscopy-guided gastrointestinal procedures (FGPs) are increasingly common. However, the radiation exposure (RE) to patients undergoing FGPs is still unclear. We examined the actual RE of FGPs. Patients and methods  This retrospective, single-center cohort study included consecutive FGPs, including endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), enteral stenting, balloon-assisted enteroscopy, tube placement, endoscopic injection sclerotherapy (EIS), esophageal balloon dilatation and repositioning for sigmoid volvulus, from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm 2 ), and fluoroscopy time (FT, min) for each procedure. Results  In total, 3831 patients were enrolled. Overall, 2778 ERCPs were performed. The median AK, DAP, and FT were as follows: ERCP: 109 mGy, 13.3 Gycm 2 and 10.0 min; self-expandable enteral stenting (SEMS): 62 mGy, 12.4 Gycm 2 and 10.4 min; tube placement: 40 mGy, 13.8 Gycm 2 and 11.1 min; balloon-assisted enteroscopy: 43 mGy, 22.4 Gycm 2 and 18.2 min; EUS cyst drainage (EUS-CD): 96 mGy, 18.3 Gycm 2 and 10.4 min; EIS: 36 mGy, 8.1 Gycm 2 and 4.4 min; esophageal balloon dilatation: 9 mGy, 2.2 Gycm 2 and 1.8 min; and repositioning for sigmoid volvulus: 7 mGy, 4.7 Gycm 2 and 1.6 min. Conclusion  This large series reporting actual RE doses of various FGPs could serve as a reference for future prospective studies.

The diagnostic reference levels (DRLs) are one of several effective tools for optimizing nuclear medicine examinations and reducing patient exposure. With the advances in imaging technology and alterations of examination protocols, the DRLs must be reviewed periodically. The first DRLs in Japan were established in 2015, and since 5 years have passed, it is time to review and revise the DRLs. We conducted a survey to investigate the administered activities of radiopharmaceuticals and the radiation doses of computed tomography (CT) in hybrid CT accompanied by single photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. We distributed a Web-based survey to 915 nuclear medicine facilities throughout Japan and survey responses were provided by 256 nuclear medicine facilities (response rate 28%). We asked for the facility's median actual administered activity and median radiation dose of hybrid CT when SPECT/CT or PET/CT was performed for patients with standard habitus in the standard protocol of the facility for each nuclear medicine examination. We determined the new DRLs based on the 75th percentile referring to the 2015 DRLs, drug package inserts, and updated guidelines. The 2020 DRLs are almost the same as the 2015 DRLs, but for the relatively long-lived radionuclides, the DRLs are set low due to the changes in the Japanese delivery system. There are no items set higher than the previous values. Although the DRLs determined this time are roughly equivalent to the DRLs used in the US, overall they tend to be higher than the European DRLs. The DRLs of the radiation dose of CT in hybrid CT vary widely depending on each imaging site and the purpose of the examination.

BACKGROUND: ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223. METHODS: Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint. RESULTS: Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6-not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7-NE) (HR = 0.907, 95% CI 0.501-1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively. CONCLUSIONS: In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: NCT02043678.

INTRODUCTION: Recently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan. METHODS AND ANALYSIS: This is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose-area product (Gycm2) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. ETHICS AND DISSEMINATION: Approval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the opt-out method of each hospital website. TRIAL REGISTRATION NUMBER: The UMIN Clinical Trials Registry, UMIN000036525.

Targeted radionuclide therapy with high-dose radioisotopes should be performed in isolation rooms. Patients can be released only after radioactivity remaining in their bodies becomes less than the limits determined by the release criteria in order to secure public protection. Patients are asked to stay in isolation rooms for a few days. Physicians often face difficulties to carry out therapy in patients with limited activities of daily living and those undergoing hemodialysis, and have to avoid therapy in such cases. The Japanese Society of Nuclear Medicine conducted a nationwide survey in order to find out the actual situation. The survey results should reflect future improvement of therapeutic environment in collaborating with related societies and administrative bodies.

We present the guideline for use of yttrium-90-labeled anti-P-cadherin antibody injection for radionuclide therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine. Treatment using yttrium-90-labeled anti-P-cadherin antibody injection in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown here are considered internationally useful as well. Only the original Japanese version is the formal document.

Purpose: Radionuclide therapy (RNT) involves the selective delivery of radiation, emitted from radionuclides to tumors or target organs. The techniques of RNT are increasingly being used for the treatment of various tumors. The purpose of this article is to report on the current state of RNT, to clarify the issues of radiation protection associated with RNT, and to show future prospects. Results and conclusions: Medical exposure of patients has unique features; application of dose limits is not undertaken, and justification and optimization do apply but in a different way from in other exposures. The expanding use of RNT has raised concern regarding potential carcinogenic and leukemogenic effects and research on second primary cancer after RNT have been developing. RNT combined with imaging and dosimetry and featuring a theranostic approach is undergoing a significant expansion, and such dosimetry-based treatment planning leads to individualization, or personalization, which is likely to improve the effectiveness and safety of patient management in RNT.

OBJECTIVE. The purpose of this study was to characterize the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison with an ordered subset expectation maximization (OSEM) reconstruction algorithm and to determine its optimal penalization factor (expressed as a beta value) for clinical use. MATERIALS AND METHODS. FDG PET/CT scans of 46 patients with lung cancer were reconstructed using OSEM and BPL with beta values of 200, 300, 400, 500, and 1000. The liver signal-to-noise ratio, mean standardized uptake value (SUVmean) of the liver, and maximum standardized uptake value (SUVmax) and SUVmean of the cancers were measured. Tumors were categorized into three size groups, and the percentage difference in the tumor SUVmax between OSEM and BPL with a beta value of 200 as well as the percentage difference in the SUVmax between BPL with a beta value of 200 and BPL with a beta value of 1000 were calculated. Image quality was assessed by visual scoring. RESULTS. BPL showed a significantly higher liver signal-to-noise ratio than OSEM, except for BPL with a beta value of 200. The liver SUVmean showed no statistical difference among all algorithms. The SUVmax and SUVmean of tumors decreased as the beta value increased. BPL with a beta value of 200 produced a significantly higher tumor SUVmax than did OSEM (p < 0.01), and BPL with a beta value of 400, 500, or 1000 produced a significantly lower tumor SUVmax than did OSEM (p < 0.01). Visual analysis showed the highest and lowest scores for BPL with beta values of 500 and 200, respectively. In the small size group, the percentage difference in the SUVmax between OSEM and BPL with a beta value of 200 and the percentage difference in the SUVmax between BPL with a beta value of 200 and BPL with a beta value of 1000 were significantly larger than that in the other size groups (p < 0.01). CONCLUSION. The BPL algorithm improves image quality without compromising image quantification. A beta value of 500 appeared to be optimal in this study. Smaller tumors were more influenced by BPL.

BACKGROUND: The α-emitting radionuclide radium-223 (223Ra) is widely used for the treatment of bone metastasis in patients with castration-resistant prostate cancer. However, 223Ra decays into radon-219 (219Rn) which is a noble-gas isotope, and 219Rn may escape from patients treated with 223Ra via their respiration. In this study, we quantified the amount of 219Rn contained in the breath of patients treated with 223Ra to estimate its effect on the internal exposure dose of caregivers. METHODS: A total of 12 breath samples were collected using a breath collection bag from a total of six patients treated with 223RaCl2. Approximately 300 mL of exhaled breath was collected in a breath bag at 1 min and at 5 min after the start of 223RaCl2 administration. The contents of each bag were measured using an HPGe detector, and the amount of 219Rn was quantified based on the detection of the γ peak of 211Bi, which is a descendant nuclide of 219Rn, persisting in the breath bag. The effective dose to caregivers arising from the inhalation of 219Rn was estimated by referring to the scenario for the calculation of release criteria established for 131I therapy in Japan. RESULTS: A small peak for the 351-keV γ ray of 211Bi originating from the exhalation of 219Rn was observed. Using the observed γ peak of 211Bi, the average amounts of 219Rn per unit breath volume at 1 min and 5 min after the start of 223RaCl2 administration were calculated as 90 ± 56 Bq/mL and 28 ± 9 Bq/mL, respectively. The effective dose of 219Rn to caregivers was estimated to be 3.5 μSv per injection. CONCLUSIONS: The amount of 219Rn in the exhaled breath of patients treated with 223RaCl2 was quantitatively calculated using breath collection bags. The internal radiation exposure of caregivers from 219Rn in the exhaled breath of patients treated with 223RaCl2 is relatively small.

Radionuclide therapy (RNT) stands on the delivery of radiation to tumors or non-tumor target organs using radiopharmaceuticals that are designed to have specific affinity to targets. RNT is recently called molecular radiotherapy (MRT) by some advocators in order to emphasize its characteristics as radiotherapy and the relevance of dosimetry-guided optimization of treatment. Moreover, RNT requires relevant radiation protection standards because it employs unsealed radionuclides and gives therapeutic radiation doses in humans. On the basis of these radiation protection standards, the development and use of radiopharmaceuticals for combined application through diagnostics and therapeutics lead to theranostic approaches that will enhance the efficacy and safety of treatment by implementing dosimetry-based individualization.

BACKGROUND: Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. METHODS: Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. RESULTS: Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). CONCLUSIONS: In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.

Radium-223 dichloride (Ra-223) is the first targeted alpha therapy approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastasis. Ra-223 improved overall survival in the international Phase III ALSYMPCA (ALpharadin in SYMPtomatic Prostate Cancer) study. Ra-223 was also demonstrated to be efficacious and safe in Japanese patients in Phase I and Phase II clinical trials. Ra-223 was approved in Japan for the treatment of patients with CRPC with bone metastasis in 2016. The conduct of clinical studies with radionuclides in Japan involves mandatory compliance with local and international regulations pertaining to radiation protection. Without an existing Japanese framework for the handling of α-emitters in clinical practice, we encountered many challenges to initiate the clinical studies. Therefore, we started on a project to determine best practice on the use of Ra-223 in clinical studies. For this project, we evaluated all applicable laws and regulations on the use of radionuclides in medicine, then examined whether and how the α-emitter Ra-223 could meet these legal and regulatory requirements. This included how to approach the matter of discharging patients administered Ra-223 from hospital and radiation protection for caregivers, general public and medical care professionals. Subsequently, we published Manual on the proper use of radium-223 dichloride injection in clinical trials that summarized the essential requirements necessary to allow the safe use of Ra-223 in clinical trials in Japan. As the result, we succeeded in demonstrating that clinical trials of an α-emitter, Ra-223, could be implemented safely in Japan. Our experience in Japan highlights the importance of a multidisciplinary team-based approach and continued professional training in a clinical setting. This article summarizes the rationale behind the development of this manual. We hope that by sharing our experience and information, we can help other countries considering the introduction of radionuclides for clinical use, and support the future development of radionuclide therapies in a safe and effective manner.

Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most frequently used image-guided procedures in gastrointestinal endoscopy. Post-ERCP pancreatitis is an important concern, and prophylaxis, cannulation and other related technical procedures have been well documented by endoscopists. In addition, medical radiation exposure is of great concern in the general population because of its rapidly increasing frequency and its potential carcinogenic effects. International organizations and radiological societies have established diagnostic reference levels, which guide proper radiation use and serve as global standards for all procedures that use ionizing radiation. However, data on gastrointestinal fluoroscopic procedures are still lacking because the demand for these procedures has recently increased. In this review, we present the current status of quality indicators for ERCP and the methods for measuring radiation exposure in the clinical setting as the next quality indicator for ERCP. To reduce radiation exposure, knowledge of its adverse effects and the procedures for proper measurement and protection are essential. Additionally, further studies on the factors that affect radiation exposure, exposure management and diagnostic reference levels are necessary. Then, we can discuss how to manage medical radiation use in these complex fluoroscopic procedures. This knowledge will help us to protect not only patients but also endoscopists and medical staff in the fluoroscopy unit.

Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well. Only the original Japanese version is the formal document.

BACKGROUND/AIM: 18F-misonidazole positron emission tomography (FMISO PET)/computed tomography (CT) obtained before and during radiotherapy (RT) was analyzed as to whether it could predict clinical outcome. PATIENTS AND METHODS: Twenty-two patients were included. FMISO PET/ CT was performed twice before RT and at a dose of approximately 20 Gy/10 fractions. FMISO maximum standardized uptake values (SUVmax), the tumor-to-muscle ratios (T/M), and hypoxic volume (HV) in gross target volumes were measured. RESULTS: Of the 22 tumors, 18 had hypoxic areas (SUVmax ≥1.60) before RT. SUVmax, T/M, and HV on the first PET/CT were significantly correlated with initial tumor response, although the values during RT were not related to the response. The overall survival and loco-regional control rates of patients below cut-off values were significantly better than those above the cut-off values. CONCLUSION: Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome.

BACKGROUND: Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases. METHODS: In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period. RESULTS: Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was -19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%). CONCLUSIONS: Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01929655.

BACKGROUND: Radiation therapy with radium-223 dichloride improves overall survival, reduces symptomatic skeletal events in Caucasian patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is well tolerated. We report here the results of the first efficacy and safety study of radium-223 dichloride in a Japanese population. METHODS: In this open-label, uncontrolled, non-randomized, phase I trial, radium-223 dichloride was given to Japanese patients with CRPC and ≥2 bone metastases in 4-week cycles. The patients were divided into three cohorts, with cohort 1 and the expansion cohort receiving injections of radium-223 dichloride [55 kBq/kg body weight (BW)] every 4 weeks (Q4W) for up to six injections, and cohort 2 receiving an initial single radium-223 dichloride injection of 110 kBq/kg BW followed by up to five injections of 55 kBq/kg BW Q4W. Safety was determined via adverse event (AE) reporting, and biochemical bone markers were assessed for treatment efficacy. RESULTS: In total 19 patients received at least one dose of radium-223 dichloride and 18 patients experienced at least one treatment-emergent AE (TEAE) of which the most common were anemia, thrombocytopenia, and lymphocytopenia. Serious AEs were reported in three patients but none were drug-related. In the patients of cohort 1 + expansion cohort (55 kBq/kg BW Q4W treatment; n = 16), prostate-specific antigen levels remained stable or slightly increased while the bone alkaline phosphatase (ALP) level significantly decreased. The response rates of bone ALP (≥30 and ≥50% reductions) were 81.8 and 36.4% at week 12, and 81.3 and 50.0% at the end of treatment. CONCLUSIONS: Radium-223 dichloride was well tolerated in these Japanese patients and, at a dose of 55 kBq/kg BW, efficacy on biomarkers was as expected. The outcomes in Japanese patients were consistent with those reported in other non-Japanese populations. TRIAL REGISTRATION: ClinicalTrials.gov record NCT01565746.

The goal of this study is to develop a more appropriate shielding calculation method for computed tomography (CT) in comparison with the Japanese conventional (JC) method and the National Council on Radiation Protection and Measurements (NCRP)-dose length product (DLP) method. Scattered dose distributions were measured in a CT room with 18 scanners (16 scanners in the case of the JC method) for one week during routine clinical use. The radiation doses were calculated for the same period using the JC and NCRP-DLP methods. The mean (NCRP-DLP-calculated dose)/(measured dose) ratios in each direction ranged from 1.7 ± 0.6 to 55 ± 24 (mean ± standard deviation). The NCRP-DLP method underestimated the dose at 3.4% in fewer shielding directions without the gantry and a subject, and the minimum (NCRP-DLP-calculated dose)/(measured dose) ratio was 0.6. The reduction factors were 0.036 ± 0.014 and 0.24 ± 0.061 for the gantry and couch directions, respectively. The (JC-calculated dose)/(measured dose) ratios ranged from 11 ± 8.7 to 404 ± 340. The air kerma scatter factor κ is expected to be twice as high as that calculated with the NCRP-DLP method and the reduction factors are expected to be 0.1 and 0.4 for the gantry and couch directions, respectively. We, therefore, propose a more appropriate method, the Japanese-DLP method, which resolves the issues of possible underestimation of the scattered radiation and overestimation of the reduction factors in the gantry and couch directions.

Objective The association between left ventricular (LV) dyssynchrony parameters, given by phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and acquisition orbits is unclear. The aim of this study was to assess the dependence of LV dyssynchrony parameters on acquisition orbits. Methods Ninety-nine patients who underwent Tl-201-gated SPECT MPI were categorized into minor hypoperfusion or major hypoperfusion groups. Forty-four patients who underwent Tc-99m-tetrofosmin-gated SPECT MPI were categorized into minor hypoperfusion or major hypoperfusion groups. The major hypoperfusion group with Tl-201 was divided into inferior or non-inferior wall hypoperfusion subgroups, and anteroseptal or non-anteroseptal wall hypoperfusion subgroups. Gated SPECT MPI data over a 360A degrees acquisition orbit (360A degrees images) and a 180A degrees acquisition orbit (180A degrees images) were reconstructed, and histogram bandwidth (HBW) and phase standard deviation (PSD) were compared. Results Between 360A degrees and 180A degrees images with Tl-201, there were significant differences in HBW and PSD both globally (HBW 34.8 +/- 16.6 vs. 29.1 +/- 10.2; PSD 8.8 +/- 4.9 vs. 7.0 +/- 2.3, p < 0.05 for both) and in the inferior wall (HBW 29.5 +/- 15.5 vs. 23.3 +/- 9.0; PSD 7.6 +/- 4.6 vs. 5.6 +/- 2.4, p < 0.001 for both) in the major hypoperfusion group, and also in the inferior wall in all subgroups of the major hypoperfusion group. In contrast, no segment had any significant differences in HBW or PSD between 360A degrees and 180A degrees images with Tc-99m. Conclusion Differences in acquisition orbit had a significant influence on HBW and PSD with Tl-201-gated SPECT MPI in the inferior wall in patients with major hypoperfusion myocardium.

Background Clinical results of computed tomography (CT) simulations and [F-18]-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT simulations were compared retrospectively. Materials and methods Between 2006 and 2011, [F-18]FDG PET/CT simulation was performed on 68 consecutive patients with pharyngeal cancers (PET/CT group). As an historical control, conventional CT simulation was performed on 56 consecutive patients with pharyngeal cancer between 2000 and 2006 (CT group). In the PET/CT group, the primary sites were nasopharynx (NPC), oropharynx (OPC), and hypopharynx (HPC) in 35, 20, and 13 patients, respectively; in the CT group, the primary sites were NPC, OPC, and HPC in 21, 17, and 18 patients, respectively. All but five patients in the PET/CT group were treated with intensity modulated radiation therapy (IMRT). Results In the PET/CT group, TNM and clinical stages changed in 11 (16 %) and eight (12 %) patients, respectively. Although the 5-year overall survival (OS) rates for the PET/CT and the CT groups were 80 and 64 %,respectively (p = 0.0420), this result may be attributable to the background difference between the two groups. Similarly, the 5-year locoregional control rates of the two groups were 82 and 70 %, respectively (p = 0.0501). Notably, marginal recurrences around the planning target volume (PTV) were only noted in four CT group patients. Conclusion PET/CT simulation was useful for delineating an accurate clinical target volume (CTV) of pharyngeal cancer, and its clinical results were satisfactory.

BACKGROUND: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is now a routine procedure for the management of cancer patients. Intravenous administration of FDG is sometimes halted due to troubles. In such cases, estimations of the FDG dosage injected prior to halting administration may be helpful. We have established a method of estimating the activity of FDG to patients on the basis of the dose equivalent rate on the surface of the right temporal region of the head. The correlation of actual administered dosage with independent variables, such as the dose equivalent rate on the right temporal region of the head, age, sex, and body weight, was analyzed using multiple regression analysis to obtain linear, quadratic, and cubic regression equations. RESULTS: When entering independent variables, the cubic regression equation could be used to estimate an administered dosage with an accuracy of ±10 % for 62 % of all patients and ±20 % for 90 % of all patients. CONCLUSIONS: We conclude that this method is useful for estimating the administered dosage from the dose equivalent rate on the temporal region of the head.

医療放射線に関連した学会・団体が、医療被ばく研究情報ネットワーク(Japan Network for Research and Information on Medical Exposure:J-RIME)の枠組みにて協働して診断参考レベルの設定に取り組み、2015年6月7日に「診断参考レベル2015(Japan DRLs 2015)」(以下、DRLs2015)を公表した。これに含まれる6つのモダリティの1つに核医学検査がある。核医学検査の診断参考レベルは、全国のすべての核医学診療施設を対象にして調査を実施し、その集計結果に基づいて「実投与量」として設定したものである。また、小児の核医学検査における放射性薬剤の適正投与量の設定も重要な課題であった。これについては、診断参考レベルとは別の概念に基づいて検討され、「小児核医学検査適正施行のコンセンサスガイドライン」に示された。したがって、現在、成人の適正投与量についてはDRLs2015、小児の適正投与量については「小児核医学検査適正施行のコンセンサスガイドライン」に規定されている仕組みとなっており、この2つの適正投与量とその内容を十分に理解して核医学検査を実施することが要である。これらの適正投与量が公表(2013〜2015年)された後、関連した学会・団体は学術集会、機関誌、Webサイトなどを通じてその普及に努めている。(著者抄録)

The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine. A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form. Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of Tc-99m-MDP and Tc-99m-HMDP: bone scintigraphy, Tc-99m-HM-PAO, Tc-99m-ECD and I-123-IMP: cerebral blood flow scintigraphy, Tc-99m-Tetrofosmin, Tc-99m-MIBI and Tl-201-Cl; myocardial perfusion scintigraphy and F-18-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq (Tc-99m-MDP and Tc-99m-HMDP: bone scintigraphy), 740 MBq (Tc-99m-ECD and Tc-99m-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq (Tc-99m-Tetrofosmin and Tc-99m-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy (Tc-99m-MDP and Tc-99m-HMDP), cerebral blood flow scintigraphy (Tc-99m-HM-PAO) and myocardial perfusion scintigraphy (Tc-99m-Tetrofosmin and Tc-99m-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity. This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

我が国では急激な甲状腺癌の増加やRI内用療法施設の実稼働ベッド数の減少などから、RI内用療法施設への入院待ち待機時間が延長し地域格差が広がっており、その現状はがん対策推進基本計画がめざす「医療の均てん化」とはほど遠い状況にある。2015年国会においてRI内用療法に関連する質問主意書が提出され、これに対しRI内用療法は重点的に取り組むべき課題であるとの政府答弁がなされており、今後の研究・診療の推進等が期待されている。本稿では医療経済的考察も含めて我が国におけるRI内用療法の現状と問題点をとりまとめ、甲状腺癌の将来的な疾病状況を予測の上、これに対応可能なRI内用療法環境を提示し、欧米諸国の現状との比較も交えて、我が国のRI内用療法のあるべき将来像を見据えた提言を行う。(著者抄録)

The goal of this study was to clarify whether binding potential (BP) images using C-11-Pittsburgh compound B (C-11-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose C-11-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. Methods: Static and BP images were constructed for 85 consecutive patients with cognitive impairment after C-11-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among C-11-PiB-positive, C-11-PiB-equivocal, and C-11-PiB-negative groups. Results: Forty-three scans were visually assessed as C-11-PiB-positive in both the static and the BP images. Ten scans were C-11-PiB-equivocal in the static images. In 8 of them, the BP images were C-11-PiB-positive, whereas the other 2 were C-11-PiB-equivocal. Thirty-two scans were assessed as C-11-PiB-negative in the static images. In the BP images, 4 were C-11-PiB-positive and 2 were C-11-PiB-equivocal. The mean gray matter uptake of C-11-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the C-11-PiB-positive, C-11-PiB-equivocal, and C-11-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the C-11-PiB-negative and C-11-PiB-equivocal groups, whereas it was higher in the C-11-PiB-positive group. Conclusion: C-11-PiB PET BP images can clarify visual interpretation of clinical static C-11-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that C-11-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings.

Background: The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of In-111-ibritumomab tiuxetan (Zevalin (R)) and tumor accumulation of F-18-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin's lymphoma patients receiving Y-90-ibritumomab tiuxetan (Zevalin (R)) therapy. Methods: Sixteen patients with histologically confirmed non-Hodgkin's B-cell lymphoma who underwent Y-90-ibritumomab tiuxetan therapy along with In-111-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of In-111-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and In-111-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results: A positive correlation was observed between the FDG SUVmax and accumulation of In-111-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in In-111-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while In-111-ibritumomab tiuxetan demonstrated skewness of 0.58 +/- 0.16 and 0.73 +/- 0.24 (p < 0.05), kurtosis of 2.39 +/- 0.32 and 2.78 +/- 0.53 (p < 0.02), and AUC-CSH of 0.37 +/- 0.04 and 0.34 +/- 0.05 (p < 0.05) for responders and non-responders. Conclusions: Pretherapeutic FDG accumulation was predictive of the tumor response in Y-90-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of In-111-ibritumomab tiuxetan was correlated with the tumor response.

We have encountered occasional equivocal findings when assessing cerebral cortical amyloid retention with C-11-Pittsburgh compound B (PiB) PET. We investigated the diagnostic significance of equivocal PiB PET findings. This retrospective study included 101 consecutive patients complaining of cognitive disorders (30 Alzheimer's disease, 25 mild cognitive impairment, 8 Lewy body disease, 7 frontotemporal lobar degeneration, 31 others) who underwent both C-11-PiB PET and F-18-fluorodeoxy-d-glucose (FDG) PET. We visually classified PiB-positive, PiB-equivocal or PiB-negative ratings according to cortical uptake. For quantitative assessments of PiB PET, standard uptake values referred to cerebellar cortex (SUVR) were calculated in regional template volume of interests (frontal, temporoparietal, precuneus/posterior cingulate cortex, cerebral white matter and cerebellar cortex). The results of visual assessment were compared with the regional and mean cortical SUVRs and cortical-to-white matter ratio of PiB uptake, as well as clinical and FDG PET findings. Among the 101 scans, 41 were PiB negative, 11 were PiB equivocal, and 49 were rated PiB positive in the visual assessments. The mean cortical SUVR and cortical-to-white matter ratio were 0.97 +/- A 0.07 and 0.57 +/- A 0.21 in PiB-negative, 1.51 +/- A 0.17 and 0.75 +/- A 0.06 in PiB equivocal and 2.10 +/- A 0.33 and 0.97 +/- A 0.11 in PiB-positive group, respectively. Nine of 11 subjects with PiB-equivocal findings had cognitive impairments and FDG distribution compatible with Alzheimer's disease or dementia with Lewy bodies. We considered equivocal visual findings on PiB PET equivalent to PiB-positive with slight cortical uptake. In addition, slight cortical amyloid deposits were considered to cause cerebral metabolic abnormality and cognitive impairment. Although mean cortical SUVR was more sensitive than visual assessment because of low cortical-to-white matter contrast due to non-specific accumulation in white matter, it is important not to overlook small amounts of cortical uptake of PiB in visual inspection for exact diagnosis.

The applicability of the activation of an NaI scintillator for neutron monitoring at a clinical linac was investigated experimentally. Thermal neutron fluence rates are derived by measurement of the I-128 activity generated in an NaI scintillator irradiated by neutrons β-rays from I-128 are detected efficiently by the NaI scintillator. In order to verify the validity of this method for neutron measurement, we irradiated an NaI scintillator at a research reactor, and the neutron fluence rate was estimated. The method was then applied to neutron measurement at a 10-MV linac (Varian Clinac 21EX), and the neutron fluence rate was estimated at the isocenter and at 30 cm from the isocenter. When the scintillator was irradiated directly by high-energy X-rays, the production of I-126 was observed due to photo-nuclear reactions, in addition to the generation of I-128 and Na-24. From the results obtained by these measurements, it was found that the neutron measurement by activation of an NaI scintillator has a great advantage in estimates of a low neutron fluence rate by use of a quick measurement following a short-time irradiation. Also, the future application of this method to quasi real-time monitoring of neutrons during patient treatments at a radiotherapy facility is discussed, as well as the method of evaluation of the neutron dose.

There is evidence that some cases of patients with dementia with Lewy bodies (DLB) can demonstrate Alzheimer disease (AD) like reduced glucose metabolism without amyloid deposition. The aim of this study was to clarify whether regional hypometabolism is related to amyloid deposits in the DLB brain and measure the degree of regional hypometabolism. Ten consecutive subjects with DLB and 10 AD patients who underwent both Pittsburgh compound B (PiB)-PET and F-18-fluoro-2-deoxyglucose (FDG)-PET were included in this study. Regional standardized uptake value ratio (SUVR)s normalised to cerebellar cortices were calculated in the FDG- and PiB-PET images. All AD patients and five DLB patients showed amyloid deposits (PiB positive). In the DLB group the parietotemporal and occipital metabolism were significantly lower than those in the AD group but there was no difference between the posterior cingulate hypometabolism between DLB and AD groups. There were no differences in regional glucose metabolism between PiB positive and negative DLB patients. In the DLB brain, it is suggested that decreased regional glucose metabolism is unrelated to amyloid deposits, although the hypometabolic area overlaps with the AD hypometabolic area and the degree of parietotemporal and occipital hypometabolism in DLB brain is much larger than that in AD brain.

To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISOPET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (=1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of =1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO =1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of =1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0-0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT. © The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.

短寿命かつ多重α・β崩壊を系列で行う²²³Ra薬剤の骨腫瘍疼痛治療への適用が日本でも開始されようとしているが，²²³Ra薬剤の管理に関わる知見はほとんど蓄積されていない。<br>本調査では²²³Ra薬剤による飛沫汚染の管理に関する実験を行った。実験の結果，広口GMサーベイメータは汚染の管理に非常に有効に機能するのに対して，NaI(Tl)シンチレーションサーベイメータは検出限界を考慮する必要があるとの結論を得た。

The purpose of this study was to develop and evaluate a new method for respiratory gated pulmonary perfusion SPECT (RGPS) based on dynamic acquisition without using an external tracking device (ETD) or list-mode data acquisition. In the phantom study, our method used a dynamic sequence technique, which was specified by sequences of 50-ms acquisition during 30 s per view of SPECT instead of using an ETD. For this purpose, we created a computer program that identified respiratory phases by calculating the center of activity (COA) in each dynamic frame image. We compared RGPS using the dynamic sequence acquisition (RGPS-DS) and RGPS using ETD (RGPS-ETD) in phantom studies employing a cylinder phantom filled with technetium-99m solution attached to an instrument providing a simple harmonic motion. In the patient study, RGPS-DS was applied to data collected from 3 patients during a routine study of Tc-MAA pulmonary perfusion SPECT. In the phantom study, the calculation of COA indicated a good agreement between RGPS-DS and RGPS-ETD. With an oscillatory phantom movement amplitude of 30 mm, the amplitudes determined by RGPS-DS and RGPS-ETD (28.36 and 27.58 mm, respectively) were identical on considering a pixel size of 4.66 mm for reconstructed SPECT images. In the patient study, applicability of our method to patient data was demonstrated. We have showed the feasibility of our method to obtain RGPS without ETD, and conclude that RGPS-DS may be an innovative and efficient technique in respiratory gated pulmonary perfusion SPECT. Further studies with a larger number of patients should demonstrate the accuracy of our method.

Purpose: To prospectively evaluate the feasibility of using the "iliac wing sign (IWS)" as an indicator of bone and/or soft-tissue injury of the pelvis and hips on magnetic resonance (MR) imaging. IWS means edema of the iliacus muscle attachment entering the iliac wing that is visualized as a linear high signal intensity on fat-suppressed T2-weighted MR images. Methods: Consecutive 106 patients who complained of hip pain were enrolled in this study. We evaluated the correlation between IWS and bone and/or soft-tissue injury of the pelvis and hips using Fisher's exact test. Further, performance parameters of sensitivity, specificity, accuracy, the positive predictive value (PPV), and negative predictive value (NPV) of IWS were calculated. Results: Thirty-eight of the 106 (36%) patients had bone and/or soft-tissue injury. Twenty-seven of these 38 (71%) patients with injury showed a positive IWS, while only 11 of 68 (16%) patients without injury showed a positive IWS (p < .0001). IWS, thus, yielded a sensitivity of 71%, specificity of 84%, accuracy of 79%, positive predictive value (PPV) of 71%, and negative predictive value (NPV) of 84%. Conclusion: In cases with a positive IWS, the careful interpretation of MR images is needed because injury presence is highly likely, as suggested by the relatively high sensitivity and PPV. IWS absence may mean a low probability of injury because of the high specificity and NPV. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to elucidate the regional differences between brain perfusion single photon emission computed tomography (SPECT) images reconstructed with a uniform attenuation correction using Chang's method (AC-Chang) and a non-uniform attenuation correction with CT using SPECT/CT (AC-CT). SPECT images of a phantom with and without head holder were obtained, and reconstructed images of AC-Chang and AC-CT were compared. Twenty-eight consecutive patients with brain disease examined by SPECT/CT brain perfusion imaging were selected, and images were reconstructed with AC-Chang and AC-CT. The AC-Chang and AC-CT reconstructed images were then compared by voxel-based analysis using three-dimensional stereotactic surface projections. Counts in the frontal area of the AC-Chang phantom image with head holder were higher than those in the posterior area. Counts in the frontal area of the AC-Chang clinical images were significantly higher than those in the AC-CT images, while the counts in the margin of the frontal lobe and posterior margin of the parietal, occipital cortices and cerebellum of the AC-Chang images were significantly lower. Relative frontal perfusion was 5.0% higher and relative cerebellar perfusion was 4.6% lower in the AC-Chang images relative to the AC-CT images, on average. We demonstrated the frontal dominant hyper-perfusion and parieto-occipital and cerebellar hypo-perfusion in brain SPECT images reconstructed with AC-Chang compared to those reconstructed with AC-CT. We suggest that to obtain an accurate attenuation-corrected brain perfusion SPECT image, attenuation correction by Chang's method is inadequate.

[Abstract] Monoclonal antibodies have markedly changed the treatment possibilities for patients with indolent B-cell lymphoma. ^<90>Y-Ibritumomab tiuxetan (Zevalin) is the first radioimmunotherapy (RIT) agent approved for the treatment of relapsed and refractory indolent lymphoma patients. In most cases, the maximum clinical response were observed two to three months after RIT. Treatment with ^<90>Y-ibritumomab tiuxetan may have potential late effects in some cases of relapsed follicular lymphomas, and we must be careful to start the next treatment after RIT.

Purpose To clarify the change in the fluorodeoxyglucose (FDG) uptake by the bone marrow over time after administration of granulocyte colony-stimulating factor (G-CSF), we evaluated the correlation between the interval from the last day of administration of G-CSF to positron emission tomography/computed tomography (PET/CT) study and spinal bone marrow accumulation in patients with non-Hodgkin's lymphoma. Methods A total of 127 patients with confirmed non-Hodgkin's lymphoma who underwent FDG PET within 60 days from the last administration of G-CSF were retrospectively reviewed. Thirty age-matched and sex-matched healthy controls were also included to evaluate physiological FDG uptake. PET/CT examinations were retrospectively reviewed, and maximum standardized uptake value (SUV(max)) was measured by placing volumetric regions of interest over each thoracic and lumbar vertebra on PET images referring to CT images. Bone marrow SUV was defined as the mean SUV(max) of the vertebra. The correlation between the interval after G-CSF and the bone marrow SUV was plotted and analyzed with polynomial approximation. Results In controls, physiological bone marrow SUV of the spine was determined. In patients with lymphoma, bone marrow SUV decreased over time and reached a plateau at about 14 days after G-CSF administration, and this was higher by 5% than the plateau at 10 days. SUV declined to the 'physiological range', that is, mean+ 1 standard deviation of patients, at about 7 days. Conclusion For a PET/CT study, an interval of 10 days after G-CSF administration is recommended to minimize the influence of G-CSF on the bone marrow when evaluating treatment response in patients with non-Hodgkin's lymphoma. Nucl Med Commun 32:678-683 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Radiography is used in medical practices based on the principles of justification and optimization. Patients’ exposure doses should be kept as low as still allows for image quality that does not disturb the diagnostic processes. To optimize diagnostic radiological procedures, the international commission on radiological protection (ICRP) advocated the establishment of diagnosis reference levels (DRLs) in the new basic recommendation (Publication 103) in 2007 by stating that “The DRL should be expressed as a readily measurable patient-dose-related quantity for the specified procedure.” In th...

放射線安全を背景とした動向を踏まえ、患者被曝線量に関連する算出可能な量として単純X線撮影系での被写体入射位置における空中線量を簡易的に測定する方法(簡易測定法)を提唱した。測定手順をできる限り簡素化し、X線の被写体入射位置で空中線量を測定する方法を採用した。しかし、測定に際しては撮影条件の選択、散乱体の排除、照射野の設定、測定器の配置など測定結果に影響する因子は残るため、手順説明書やチェックシートなどの活用により、手順の標準化を行い、正確に空中線量を測定することが必要と考えられた。また、測定にはガラスバッジの支持台や撮影室の壁などからの散乱線の影響が及ばない配置が望まれるが、撮影室の状況から理想的な配置が困難な場合も想定される。

Faint brain [ (18)F]fluoro-2-deoxyglucose (FDG) uptake has sporadically been reported in patients with FDG-avid large or diffusely extended tumors. The purpose of this study was to investigate whether there is a correlation between massive tumor uptake and decreased brain uptake on FDG positron emission tomography/computed tomography (PET/CT). Sixty-five patients with histologically confirmed non-Hodgkin's lymphoma who underwent FDG-PET/CT were enrolled. Thirty control subjects were also included to evaluate normal brain FDG uptake. PET/CT examinations were retrospectively reviewed. The volumetric regions of interest were placed over lesions by referring to CT and PET/CT fusion images to measure mean standardized uptake value (SUVavg). The products of SUVavg and tumor volume were calculated as total glycolytic volume (TGV). The maximum SUV (SUVmax) and SUVavg were measured in the cerebrum and cerebellum. The values of TGV and brain FDG uptake were plotted and analyzed with a linear regression method. In the lymphoma patients, there were statistically significant negative correlations between TGV and brain SUVs. Demonstrating a significant negative correlation between TGV and brain uptake validated the phenomenon of decreased brain FDG uptake. Diversion of FDG from the brain to the lymphoma tissue may occur during the FDG accumulation process. Recognition of this phenomenon prevents unnecessary further neurological examinations in such cases.

転移性肝癌の診断において,既に原発巣がわかっている場合には,存在診断が重要であり,もし転移があれば,治療方針を決定するためにサイズ,個数を正確に評価しなければならない.転移性肝癌の検出には,造影CTで検索することが多いが,SPIO造影MRIを組み合わせることで診断能が向上する.また,近年ではGd-EOB-DTPAが発売され,より小さな病変が指摘できるようになった.FDG PET-CTは良性病変との鑑別や治療後効果判定に役立つ.胆嚢転移は非常に稀であるが,膵転移は比較的目にすることが多い.膵転移は腎細胞癌からの転移が多いが,術後10年以上の経過で見つかることも少なくなく,注意が必要である.(著者抄録)

Malignant lymphoma is the most common form of hematologic cancer, yet because of advanced methods of assessment, the traditional histology-based classification of lymphoma is insufficient for understanding lymphoma imaging. Still, radiologists should be familiar with the imaging findings in lymphoma. Integrated positron emission tomography (PET) computed tomography (CT) allows improved diagnostic accuracy, and uptake of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) can help predict response during treatment. The sensitivity and specificity of FDG PET are superior to those of gallium 67 scintigraphy in all but indolent lymphoma. Both magnetic resonance (MR) imaging and CT allow excellent assessment of bone texture, but FDG PET is superior in demonstrating bone marrow metabolic activity. Thus, FDG PET is important in both the primary diagnosis and the evaluation of therapy in lymphoma. It may be difficult to determine whether residual abnormalities seen after the completion of chemotherapy radiation therapy represent residual tumor or fibrotic tissue, but PET/CT may allow more accurate diagnosis than MR imaging or CT, thereby helping identify patients who require more intensive treatment. Some diagnostic pitfalls are encountered at FDG PET. However, anatomic CT helps localize and define disease and avoid these potential pitfalls. (c) RSNA, 2010 . radiographics.rsna.org

Purpose: Clinical applicability of a multiple-threshold method for [F-18]fluoro-2-deoxyglucose (FDG) activity in radiation treatment planning was evaluated. Methods and Materials: A total of 32 patients who underwent positron emission and computed tomography (PET/CT) simulation were included; 18 patients had lung cancer, and 14 patients had pharyngeal cancer. For tumors of cm <= 2 to 5 cm, and >5 cm, thresholds were defined as 2.5 standardized uptake value (SUV), 35%, and 20% of the maximum FDG activity, respectively. The cervical and mediastinal lymph nodes with the shortest axial diameter of >= 10 mm were considered to be metastatic on CT (LNCT). The retropharyngeal lymph nodes with the shortest axial diameter >= 5 of mm on CT and MRI were also defined as metastatic. Lymph nodes showing maximum FDG activity greater than the adopted thresholds for radiation therapy planning were designated LNPET-RTP, and lymph nodes with a maximum FDG activity of >= 2.5 SUV were regarded as malignant and were designated LNPET-2.5 SUV. Results: The sizes of gross tumor volumes on PET (GTVPET) with the adopted thresholds in the axial plane were visually well fitted to those of GTV on CT (GTVCT). However, the volumes of GTVPET were larger than those of GTVCT, with significant differences (p < 0.0001) for lung cancer, due to respiratory motion. For lung cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 29, 28, and 34, respectively. For pharyngeal cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 14, 9, and 15, respectively. Conclusions: Our multiple thresholds were applicable for delineating the primary target on PET/CT simulation. However, these thresholds were inaccurate for depicting malignant lymph nodes. (C) 2010 Elsevier Inc.

We report a case of fourth ventricular mixed germ cell tumor (GCT) in a 20-year-old man. Neuroradiological investigations revealed a fourth ventricular hemorrhagic tumor with adipose tissue. We suspected mixed GCT because adipose tissue was seen preoperatively, but mixed GCT occurring after childhood in this location has not previously been reported. We describe herein the imaging findings for mixed GCT and discuss the differential diagnoses of fourth ventricular tumors with adipose tissue.

肺癌と咽頭癌に対するPET/CTを用いた治療計画法で、多段階閾値設定法を提案し、その臨床的意義と問題点をあきらかにした。

The quality of the portal verification radiographs produced using the enhanced-contrast localisation (EC-L) Fast cassette-EC-L film (F-EC) combination and the EC-L Oncology cassette-EC-L film (O-EC) combination was investigated fundamentally and clinically. A computerised radiography (CR) system was used for comparison. In the clinic, portal verification radiographs produced for 22 patients with breast cancer were evaluated. The characteristic curves showed that the relative speed was 0.92 for the O-EC combination when the speed of the F-EC combination was defined to be 1, and that the average gradients were 4.76 and 4.35 for the F-EC combination and the O-EC combination, respectively. The smallest visible volumes of Burger's phantom were 50.3 mm3, 60.8 mm3 and 199.5 mm3 for the F-EC combination, the O-EC combination and the CR system, respectively, at an energy of 9 MeV, and 68.4 mm3, 74.2 mm3 and 195 mm3, respectively, at an energy of 12 MeV. In the clinic, both combinations at an energy of 6 MeV and the O-EC combination at 9 MeV showed very poor quality owing to underdensity. However the F-EC combination at an energy of 12 MeV and the O-EC combination at an energy of 15 MeV demonstrated a higher quality. When bremsstrahlung dose passing through the body is sufficient, the quality of portal verification radiography using EC-L film is appropriate for clinical use. © 2009 The British Institute of Radiology.

To investigate whether integrated fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) can differentiate benign from adrenal malignant lesions on the basis of maximum standardized uptake value (SUV(max)), tumor/liver (T/L) SUV(max) ratio, and CT attenuation value (Hounsfield Units; HU) of unenhanced CT obtained from FDG-PET/CT data. We studied 30 patients with 35 adrenal lesions (16 adrenal benign lesions, size 16 +/- A 5 mm, in 15 patients; and 19 adrenal malignant lesions, 24 +/- A 12 mm, in 15 patients) who had confirmed primary malignancies (lung cancer in 23 patients, lymphoma in 2, esophageal cancer in 2, hypopharyngeal cancer in 1, prostate cancer in 1, and 1 patient in whom lesions were detected at cancer screening). All patients underwent PET/CT at 1 h post FDG injection. Diagnosis of adrenal malignant lesions was based on interval growth or reduction after chemotherapy. An adrenal mass that remained unchanged for over 1 year was the standard used to diagnose adrenal benign lesions. Values of FDG uptake and CT attenuation were measured by placing volumetric regions of interest over PET/CT images. Adrenal uptake of SUV(max) a parts per thousand yen 2.5 was considered to indicate a malignant lesion; SUV(max) < 2.5 was considered to indicate a benign lesion. In further analysis, 1.8 was employed as the threshold for the T/L SUV(max) ratio. Unenhanced CT obtained from PET/CT data was considered positive for adrenal malignant lesions based on a CT attenuation value a parts per thousand yen 10 HU; lesions with a value < 10 HU were considered adrenal benign lesions. Mann-Whitney's U test was used for statistical analyses. SUV(max) in adrenal malignant lesions (7.4 +/- A 3.5) was higher than that in adrenal benign lesions (2.1 +/- A 0.5, p < 0.05). The CT attenuation value of adrenal malignant lesions (27.6 +/- A 11.9 HU) was higher than that of adrenal benign lesions (10.1 +/- A 12.3 HU, p < 0.05). In differentiating between adrenal benign and malignant lesions, a CT threshold of 10 HU corresponded to a sensitivity of 57%, specificity of 94%, accuracy of 74%, positive predictive value of 92% and negative predictive value of 65%. An SUV(max) cut-off value of 2.5 corresponded to a sensitivity of 89%, specificity of 94%, accuracy of 91%, positive predictive value of 94% and negative predictive value of 88%. The T/L SUV(max) ratio was 1.0 +/- A 0.2 for adrenal benign lesions and 4.5 +/- A 3.0 for adrenal malignant lesions. And T/L SUV(max) ratio cut-off value of 1.8 corresponded to a sensitivity of 85%, specificity of 100%, accuracy of 91%, positive predictive value of 100% and negative predictive value of 83%. FDG-PET/CT with additional SUV(max) analysis improves the diagnostic accuracy of adrenal lesions in cancer patients.

We have occasionally seen ring-shaped lateral ventricular nodules < 1 cm in diameter during routine brain magnetic resonance imaging (MRI). We investigated retrospectively clinical and MRI findings of the nodules. Review of radiological records was performed for 39,607 patients who underwent brain MRI between January 2001 and April 2008. Nodules were assessed for number, location, shape, and signal intensity, which was determined based on the range of signal intensity from gray to white matter on T1- and T2-weighted imaging. Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI), contrast enhancement characteristics, and serial MRI changes of nodules were assessed when available. Nine of 39,607 patients (0.023%) showed the nodules. No symptoms associated with the nodules. Among the nine patients, 11 nodules were identified (one nodule in seven patients (77.8%) and two nodules in two patients (22.2%)). Location was limited to the roof of the body for six nodules (54.5%) and the frontal horn for five patients (45.5%). All nodules (100%) were round and isointense on T1- and T2-weighted imaging. On FLAIR imaging of eight nodules, six (75%) were hyperintense, and two (25%) were isointense. On DWI of seven nodules, all nodules (100%) were isointense. None of seven nodules (0%) examined using postcontrast MRI showed enhancement. None of eight nodules (0%) examined using serial MRI (range, 4-60 months) showed changes in morphology over time. These nodules were incidentally encountered and shared similar MRI features. Although pathological confirmation was lacking in our cases, these nodules may be of nonaggressive nature.

Neuroacanthocytosis is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis in the peripheral blood. Clinical manifestations of this disorder resemble those of Huntington disease (HID). Neuroimaging features of neuroacanthocytosis are atrophy and signal intensity change of the striata on MR imaging, as in HID. We report herein the cases of 2 siblings with neuroacanthocytosis showing cerebellar atrophy as well as atrophy and signal intensity changes of striata.

The purpose of this study was to verify the shielding evaluation method for medical X-ray imaging facilities in Report No. 147 of the National Council on Radiation Protection and Measurements (NCRP). We investigated the concept of radiation protection and the major revised point in Report No. 147. The goal of radiation protection in Report No. 147 was compared with that in Japan. Using the data of the Imaging Performance Assessment of CT scanners (ImPACT) 2006 and the latest pre-installation manuals of several manufactures for different computed tomography (CT) scanner models, we verified t...

To assess whether integrated fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can improve the diagnostic accuracy of metastatic regional lymph nodes (LNs) in esophageal cancer compared with contrast enhanced CT (CECT). We examined 180 consecutive patients with esophageal cancer by integrated PET/CT between April 2006 and March 2007. Eighteen patients (M:F 14:4) underwent radical esophagectomy after evaluations by PET/CT and CECT of 5-7-mm-thick slices 70-80 s after injection. Regional LNs of esophageal cancer were retrospectively reviewed on CECT images by two blinded evaluators on the basis of the following cutoff sizes: 7 mm for all regional LNs (Protocol A), 10 mm for paratracheal LNs (Protocol B), and 7 mm for others. In addition, the maximum standardized uptake value (SUVmax) on PET/CT was evaluated for positive uptake by LNs. Of 210 LNs excised at surgery, 25 were positive and 185 were negative for metastasis at pathology. The PET/CT images identified 15 true-positive and 184 truenegative LNs, whereas CECT identified 15 true positives and 176 true negatives in Protocol A, and 14 true positives and 180 true negative in Protocol B. The sensitivity, specificity, accuracy, positive, and negative predictive values of PET/CT were respectively 60.0%, 99.5%, 94.8%, 93.8%, and 94.8%, whereas those of CECT were 60.0%, 95.1%, 91.0%, 62.5%, and 94.6% (Protocol A) and 56.0%, 97.3%, 92.4%, 73.7%, and 94.2% (Protocol B). A comparison of the two CECT protocols revealed fewer false-positive LNs in Protocol B, but slightly lower sensitivity in Protocol B than in Protocol A. Substantial numbers of false-positive LNs were determined by CECT in the paratracheal regions (6 of 9, 66.7%) and CECT revealed central necrosis in 4 of 15 (26.7%) true-positive LNs > 1.8 cm. The mean SUVmax on PET/CT was 2.9 (range 1.7-5.5) in true-positive LNs. The smallest LN metastasis detectable by PET/CT was 6 mm. Integrated PET/CT improves the PPV of regional LNs when compared with CECT.

Objective To determine an appropriate threshold value for delineation of the target in positron emission tomography (PET) and to investigate whether PET can delineate an internal target volume (ITV), a series of phantom studies were performed. Methods An ellipse phantom (background) was filled with 1028 Bq/ml of [ (18)F] fluoro-2-deoxyglucose ((18)FDG), and six spheres of 10 mm, 13 mm, 17 mm, 22 mm, 28 mm, and 37 mm in diameter inside it were filled with (18)FDG activity to achieve source-to-background (S/B) ratios of 10, 15, and 20. In static phantom experiments, an appropriate threshold value was determined so that the size of PET delineation fits to an actual sphere. In moving phantom experiments with total translations of 10 mm, 20 mm, and 30 mm and a period of oscillation of 4s, the maximum size of PET delineation with the appropriate threshold value was measured in both the axial and sagittal planes. Results In the static phantom experiments, the measured maximum (18)FDG activities of spheres of less than 22 mm were lower than 80% of the injected (18)FDG activity, and those for the larger spheres ranged from 90% to 110%. Appropriate threshold values determined for the spheres of 22 mm or more ranged from 30% to 40% of the maximum (18)FDG activity, independent of the S/B ratio. Therefore, we adopted an appropriate threshold value as 35% of the measured maximum (18)FDG activity. In moving phantom experiments, the maximum (18)FDG activity of spheres decreased significantly, dependent on the movement distance. Although the sizes of PET delineation with 35% threshold value tended to be slightly smaller (< 3 mm) than the actual spheres in the axial plane, the longest sizes in the sagittal plane were larger than the actual spheres. Conclusions When a threshold value of 35% of the measured maximum (18)FDG activity was adopted, the sizes of PET delineation were almost the same for static and moving phantom spheres of 22 mm or more in the axial plane. In addition, PET images have the potential to provide an individualized ITV.

Relapsing polychondritis is a rare autoimmune disease characterized by recurrent inflammation of cartilage in multiple sites of the body, including the auricles. Central nervous system involvement appears rare. We encountered a case of relapsing polychondritis with encephalitis that could be diagnosed by the unique appearance of the auricle with signal hyperintensity on diffusion-weighted magnetic resonance imaging.

Objective The objective of our study was to evaluate diagnostic ability and features of quantitative indices of three modalities: uptake rate on norcholesterol scintigraphy, computed tomography (CT) attenuation value, and fat suppression on chemical-shift magnetic resonance imaging (MRI) for characterizing adrenal adenomas. Methods Image findings of norcholesterol scintigraphy, CT, and MRI were reviewed for 78 patients with functioning (n = 48) or nonfunctioning (n = 30) adrenal masses. The norcholesterol uptake rate, attenuation value on unenhanced CT, and suppression on in-phase to opposed-phase MRI were measured for adrenal masses. Results The norcholesterol uptake rate, CT attenuation value, and MR suppression index showed the sensitivity of 60%, 82%, and 100%, respectively, for functioning adenomas of < 2.0 cm, and 96%, 79%, and 67%, respectively, for those of >= 2.0 cm. A statistically significant correlation was observed between size and norcholesterol uptake, and between CT attenuation value and MR suppression index. Regarding norcholesterol uptake, the adenoma-to-contralateral gland ratio was significantly higher in cortisol releasing than in aldosterone-releasing adenomas. Conclusions The norcholesterol uptake rate was reliable for characterization of adenomas among adrenal masses of >= 2.0 cm. CT attenuation value and MR suppression index were well correlated with each other, and were useful regardless of mass size.

ファントム実験で得られた回復係数(RCs)を用い、部分容積効果の影響を受けやすいリンパ節のStandardized uptake values(SUV)補正を行うことで、肺癌および食道癌での縦隔リンパ節転移の診断能が向上するか検討した。肺癌においても食道癌においても、リンパ節転移の診断には、ROC解析でsizeよりもSUVmaxとcSUVmaxでの評価の方が大きなAzを示し、高い診断能を有した。SUVmaxとcSUVmaxの比較では、補正によりAzがやや低下し、小病変の低いSUVmaxが過大に補正されて診断能を損なった可能性があった。食道癌の転移陽性リンパ節は肺癌の転移陽性リンパ節に比してsizeが小さく、SUVmaxが低い傾向があり、腫瘍ごとにリンパ節転移のsize、SUVmaxについて指標を設定する必要が考えられた。

OBJECTIVE. The purpose of our study was to evaluate whether simultaneous injection into cubital veins bilaterally at one half of the standard injection rate achieves similar hepatic and aortic enhancement on MDCT as the conventional injection rate into a single cubital vein. MATERIALS AND METHODS. Thirty-two patients underwent multiphase MDCT because they were suspected of having a hepatic tumor. Patients were assigned to one of the following two groups: group A, 100 mL of 370 mg I/mL of contrast medium injected into a unilateral cubital vein (one-route) via a 20-gauge cannula at a rate of 4 mL/s; or group B, 50 mL of contrast medium injected into the cubital veins bilaterally (two-route) via 24-gauge cannulas at 2 mL/s. Peak contrast enhancement of the liver and abdominal aorta for groups A and B was measured using regions of interest and compared; arrival time of the contrast media was also compared using a bolus-tracking system. Analysis was performed using Wilcoxon's signed rank test. RESULTS. Peak aortic enhancement of groups A and B was 367 +/- 67 H and 361 +/- 113 H (p = 0.61, not significant), respectively, and peak hepatic enhancement of groups A and B was 56 +/- 11 H and 56 +/- 16 H (p = 0.88, not significant), respectively. Mean arrival time to the aorta of group B (19.4 +/- 3.4 seconds) was significantly later compared with that of group A (15.5 +/- 3.5 seconds) (p = 0.005). CONCLUSION. The slower two-route injection produced the same aortic and hepatic enhancement as the faster one-route method with faster injection, but the arrival time of the contrast medium was later using the two-route method.

Purpose. Motion artifact is problematic in the diagnosis of Creutzfeldt-Jakob disease (CJD) because of dementia. The purpose was to compare the occurrence of this artifact between a diffusion-weighted (DW) magnetic resonance ( MR) imaging sequence and conventional sequences. Materials and methods. Ten MR examinations comprising T2- weighted, T1- weighted, DW, and fl uidattenuated inversion recovery imaging in seven CJD patients were retrospectively evaluated. The occurrence of motion artifacts on each sequence were assessed, and the examination was classifi ed into four groups as follows: group A, motion artifact not revealed on DW imaging but revealed on one or more other sequences; group B, revealed on DW imaging and one or more other sequences; group C, not revealed on any sequences; and group D, revealed on DW imaging but not on any other sequences. Results. The 10 MR examinations were classifi ed as eight group A ( 80%), one B ( 10%), one C ( 10%), and zero D ( 0%). Conclusion. Motion artifacts are likely to occur in any conventional imaging sequences in CJD, but the fastimaging ability of DW imaging can reduce this artifact. The combination of an absence of motion artifact on DW imaging and the presence on conventional sequences may be one of the frequent fi ndings of CJD.

骨軟部腫瘍を対象にFDG-PETによる診断成績について全国アンケート調査を行い,7施設から20疾患75症例のデータが寄せられた。骨肉腫,ユーイング肉腫(原始神経外胚葉腫瘍を含む),脂肪肉腫,平滑筋肉腫,血管肉腫,横紋筋肉腫,骨巨細胞腫,神経鞘腫,悪性線維性組織球症,軟骨肉腫,胞巣状軟部肉腫,類上皮肉腫,内膜間質肉腫,Hibernoma,線維肉腫,多発性骨軟骨腫,仙骨脊索腫,ランゲルハンス細胞組織球症,神経線維腫症についてのデータを分析した結果,上記の疾患すべてについて,FDG-PETは有用性が高いと考えられた。

64列MDCTの臨床画像を供覧し、その実際について述べた。

Background Alzheimer's disease and major depression are representative diseases that present forgetfulness and a depressive mood. It is often difficult to make a differential diagnosis between the two in the initial phase. Aim To evaluate the differential diagnosis method using regional cerebral blood flow patterns with a three-dimensional stereotactic surface projection technique. Methods Twenty early-elderly patients with mild and moderate forgetfulness were studied. Among them, 10 were diagnosed as having major depression (the MD group) and the other 10 as having Alzheimer's disease (the AD group). All patients underwent cerebral perfusion single photon emission computed tomography (SPECT) with [I-123] iodoamphetamine. A z-score was calculated for each pixel of the cerebral surface. Twenty-one circular regions of interest (ROIs) were placed on the z-score map. The significance of the statistical difference in ROI values between the two groups was determined by using the two-sided Mann-Whitney U-test. Results The z-scores for the lateral parietal, lateral temporal, bilateral precuneus and bilateral posterior cingulate gyrus were significantly reduced in the AD group compared with those in the MD group. The z-scores for the lateral frontal, left thalamus and bilateral medial frontal regions were significantly lower in the MD group than in the AD group. Conclusion Our study demonstrated a difference in regional cerebral blood flow patterns between the early elderly with Alzheimer's disease and those with major depression. All patients were classified into the appropriate categories using discriminant analysis and z-scores of frontal and parietal regions. Brain perfusion SPECT was a useful tool for the differential diagnosis between Alzheimer's disease and major depression.

Background: The effect of different pneumoperitoneal pressures on tumor cell distribution was investigated. Methods: Donryu rats were allocated to receive carbon dioxide pneumoperitoneum at 5, 10, or 15 mmHg for 60 min or to serve as a control. During the procedure, each rat was inoculated with radiolabeled ascites hepatoma cells via the portal vein (experiment 1) or femoral vein (experiment 2). In both experiments, the rats were killed 30, 60, 90, or 120 min after tumor cell inoculation, and the liver and lungs were extirpated for radioactivity count (n = 5 or 6 for each time point in each group). Results: In experiment 1, the percentage of injected dose (% ID) for the liver was greater than for the other three groups 120 min after tumor cell inoculation. There were no significant differences in the %IDs of the lungs at any time point among the groups. In experiment 2, there were no significant differences in the %IDs of the liver and lungs at any time point among the groups. Conclusions: These results Suggest that an elevated insufflation pressure facilitates the location of intraportally injected tumor cells in the liver, and that pulmonary location of the tumor cells may not depend on insufflation pressures in this animal model.

局所進行非小細胞肺癌において気道狭窄を伴い縦隔リンパ節腫大の著明な症例は手術適応に乏しく治療に難渋する. 今回われわれは, 気道狭窄により呼吸困難を呈し, 緊急治療を要した局所進行非小細胞肺癌患者7例を対象に, YAGレーザー治療と放射線外部照射 (60Gy～66Gy目標) の併用療法を施行した. 患者は強い呼吸困難を訴えたため原則としてYAGレーザー治療を先行し, 引き続き放射線治療が開始された. 治療開始時, 呼吸困難のために仰臥位が困難であった多くの症例は治療早期に症状が改善し, 全例治療完遂が可能であった. 治療により酸素投与は不必要で独歩移動が可能となり通常生活が可能となり, 局所制御効果も良好であった.<br>強度気道狭窄を伴う局所進行肺癌においてYAGレーザー治療併用放射線治療により気道狭窄は改善し, 高いQOLを得ることが出来た.

Objective : The purpose of this study was to obtain the convenient, synthetically useful bifunctional chelating agent, 6-(4-isothiocyanatobenzyl)-5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane, and to apply it to stable 99m Tc-labelling of monoclonal antibodies (mAbs). Methods : The chelate was synthesised by reaction of nitrobenzyl malonate and triethylenetetramine followed by alkylation by reacting with bromoacetic acid at pH 10. The amino group was converted to isothiocyanato derivative by reacting with thiophosgene at pH 2.0. Conjugation with mAbs [ (anti-carcinoembryonic antigen (CEA) and anti-epidermal growth factor receptor (EGFr)] was performed at pH 8.4 using trisodium phosphate solution by incubating at 37degreesC for 1 h and subjected to purification on size exclusion chromatography. Results : When radioimmunoconjugates were labelled with Tc-99m, the specific activity of immunoconjugates was 20-30 mCi/mg of protein and their immunoreactivity exceeded 80%. The stability in serum indicated that the metal remained bound to antibodies. Biodistribution studies in athymic mice grafted with U-87 human glioblastoma multiforme and MDA-MB-468 human breast carcinoma tumours revealed significant localisation of Tc-99m-labelled antibodies in tumours and reduced accumulation in normal organs. Conclusion : This bifunctional chelating agent is promising for immunoscintigraphy because of good tumour-to-normal organ contrast.

We report a case of esophageal carcinoma that showed extraosseous accumulation of Tc-99m-MDP in lymph node metastases to the cervical and paracardial lymph nodes. There are few cases showing abnormal extraosseous accumulation of Tc-99m-MDP in esophageal cancer lesion. The patient was a 53-year-old man with advanced esophageal cancer. Bone scintigraphy demonstrated extraosseous accumulations in left supraclavicular and paracardial lymph node metastases. The histopathological diagnosis was small cell carcinoma of the esophagus, which is a rare disease with aggressive behavior and poor prognosis. Our patient underwent 2 courses of systemic chemotherapy (CDDP + VP16), but died of rapidly growing systemic metastases 5 months after the initial treatment.

We report a case of esophageal carcinoma that showed extraosseous accumulation of 99mTc-MDP in lymph node metastases to the cervical and paracardial lymph nodes. There are few cases showing abnormal extraosseous accumulation of 99mTc-MDP in esophageal cancer lesion. The patient was a 53-year-old man with advanced esophageal cancer. Bone scintigraphy demonstrated extraosseous accumulations in left supraclavicular and paracardial lymph node metastases. The histopathological diagnosis was small cell carcinoma of the esophagus, which is a rare disease with aggressive behavior and poor prognosis. Our patient underwent 2 courses of systemic chemotherapy (CDDP + VP16), but died of rapidly growing systemic metastases 5 months after the initial treatment.

Objectives: Alzheimer's disease (AD) is diagnosed by either inspection of the brain perfusion SPECT, or three-dimensional stereotactic surface display (3D-SSP). The purpose was to compare diagnostic performances of these methods. Methods: Sixteen nuclear medicine physicians independently interpreted Tc-99m-ECD SPECT in one session and SPECT with 3D-SSP in another session without clinical information for 50 studies of AD patients and 40 studies of healthy volunteers. Probabilities of AD were reported according to a subjective scale from 0% (normal) to 100% (definite AD). Receiver operating characteristics curves were generated to calculate areas under the ROC curves (Az's) for the inspection as well as for an automated diagnosis based on a mean Z value in the bilateral posterior cingulate gyri in a 3D-SSP template. Results: Mean Az for visual interpretation of SPECT alone (0.679 +/- 0.058) was significantly smaller than that for visual interpretation of both SPECT and 3D-SSP (0.778 +/- 0.060). Az for the automated diagnosis (0.883 +/- 0.037) was. significantly greater than that for both modes of visual interpretation. Conclusions: 3D-SSP enhanced performance of the nuclear medicine physicians inspecting SPECT. Performance of the automated diagnosis exceeded that of the physicians inspecting SPECT with and without 3D-SSP.

肝のDynamic MDCTでは造影剤投与後適切な撮像時間帯でスキャンすることが不可欠である。このためには体内での造影剤の動態、および造影剤投与時の種々の因子について理解しておくことが必要である。これらの点について解説した。

Background: Few studies have examined tumor cell distribution following laparoscopic surgery for colorectal cancer. We examined the effect of carbon dioxide pneumoperitoneum on the distribution of intrasplenically injected colon cancer cells in mice. Methods: Mice were intrasplenically injected with 2 x 10(4) colon 26 cells labeled with (11I) In-oxine and were randomized to undergo pneumoperitoneum at 10 mmHg for 30 min or to receive no treatment other than anesthesia. Radioactivity of the liver, lungs, and spleen was measured 30, 60, 90, or 150 min following tumor inoculation. Results: The dynamic changes in the hepatic radioactivity were not similar between groups. However, the values were not significantly different at any time point. The radioactivity of lungs was extremely low in both groups throughout the experimental period. Conclusions: Pneumoperitoneum does not appear to cause the accumulation of intraportally spreading tumor cells in the liver, but it may affect the dynamic changes of tumor cells. Also, tumor cell localization in the lungs is negligible in both pneumopentoneum and control groups.

A case of embryonal rhabdomyosarcoma (RMS) arising from an axillary space is described. RMS is one of the most common soft-tissue neoplasms in children, but adult embryonal RMS is rare. The patient was a 55-year-old man with a tumor of the left axillary area. RMS arising from an axillary area is also uncommon. The histological diagnosis was embryonal RMS. He received irradiation combined with chemotherapy (VAC: VCR, act-D, CPA) for the primary and metastatic lesions, obtained complete remission, and has remained disease-free for over four years as of this report.

A 46-year-old woman with multiple myeloma presented with neurological symptoms in the right upper extremity. After MR imaging of the cervical spine failed to show the cause of her symptoms, Ga-67 scintigraphy demonstrated increased uptake in multiple areas including the right supraclavicular region and bilateral lower extremities. Histology of the specimen obtained from the left thigh proved soft-tissue involvement of myeloma, and extensive extramedullary involvement was diagnosed. Radiotherapy to the right supraclavicular mass relieved her symptoms. Although Ga-67 scintigraphy is generally considered of limited value in multiple myeloma, this modality contributed to the development of an appropriate strategy in this patient with extensive extramedullary involvement.

The authors examined three patients with pure primary mediastinal seminomas, all of whom had marked Ga-67 uptake on scintigraphy. The unusual presentation of sclerotic bone metastases with remarkable extraosseous soft tissue involvement was observed in one patient. Another had a seminoma associated with a multiloculated thymic cyst, which is a rare lesion.

A 46-year-old woman with multiple myeloma presented with neurological symptoms in the right upper extremity. After MR imaging of the cervical spine failed to show the cause of her symptoms, Ga-67 scintigraphy demonstrated increased uptake in multiple areas including the right supraclavicular region and bilateral lower extremities. Histology of the specimen obtained from the left thigh proved soft-tissue involvement of myeloma, and extensive extramedullary involvement was diagnosed. Radiotherapy to the right supraclavicular mass relieved her symptoms. Although Ga-67 scintigraphy is generally considered of limited value in multiple myeloma, this modality contributed to the development of an appropriate strategy in this patient with extensive extramedullary involvement.

The authors examined three patients with pure primary mediastinal seminomas, all of whom had marked Ga-67 uptake on scintigraphy. The unusual presentation of sclerotic bone metastases with remarkable extraosseous soft tissue involvement was observed in one patient. Another had a seminoma associated with a multiloculated thymic cyst, which is a rare lesion.

近年, 癌治療においてQuality of Life (QOL) の向上が重要な課題となっている. 放射線治療におけるQOL評価法はいまだ確立された方法がなく, また放射線治療が患者のQOLに与える影響も明らかにされていない. そこでわれわれはQOL調査票を用いて, 放射線治療が施行された患者のQOLの変化を調べ, QOLに及ぼす影響についた考察した. QOL調査票は厚生省粟原斑のrがん薬物療法におけるQOL調査票を使用した. 355例の成人癌患者を対象とし, QOL調査は治療開始時・中・終了時の3回行い評価した. 症例全体ではQOLスコアは治療終了時に改善が認められた. これは高齢者においても岡様の結果であった. また婦症照射例 (その多くがPS2-4) でQOLスコアの改善が顕著であった. 化学療法供用例や口腔内が照射された例ではむしろQOLスコアの悪化が見られた. 以上より放射線治療は高齢者やPS不良群でもQOLを損なわず治療可能であり, また姑息・対症照射鋼でQOLの改善が明らかであった. ただし化学療法併用群や口腔内が照射される例では, 注意深く治療する必要がある. 本調査票は放射線治療患者のQOL評価に有用である.

Objective: Frequent association between liver cirrhosis and hypoxemia. has been well documented. It is mostly attributable to intrapulmonary shunt due to dilation of pulmonary vasculature. We performed quantitative lung perfusion scintigraphy to detect an intrapulmonary shunt in cirrhosis patients. Methods: Prior to injection, Tc-99m MAA was applied to thin layer chromatography for quality control. Three cirrhosis patients who had hypoxemia were examined as well as 11 control subjects. After i.v. injection of Tc-99m MAA, whole body anterior and posterior images were taken at 5 min in patients with cirrhosis and at 8 time points up to 60 min in control subjects. Regions of interest were placed at the bilateral lungs and the whole body, and pulmonary accumulation was calculated. Results: All the control subjects demonstrated more than 90% of radioactivity in the lungs until 20 min. In contrast, all the patients showed values less than 80% at 5 min. In the cirrhosis patients with hypoxemia, the presence of intrapulmonary shunt was confirmed on quantitative lung perfusion scan. In control subjects, pulmonary accumulation of Tc-99m MAA dropped as a function of time and became less than 90% after 30 min. Conclusion: The timing of measurements is essential in evaluating intrapulmonary shunt.

Objective: Frequent association between liver cirrhosis and hypoxemia. has been well documented. It is mostly attributable to intrapulmonary shunt due to dilation of pulmonary vasculature. We performed quantitative lung perfusion scintigraphy to detect an intrapulmonary shunt in cirrhosis patients. Methods: Prior to injection, Tc-99m MAA was applied to thin layer chromatography for quality control. Three cirrhosis patients who had hypoxemia were examined as well as 11 control subjects. After i.v. injection of Tc-99m MAA, whole body anterior and posterior images were taken at 5 min in patients with cirrhosis and at 8 time points up to 60 min in control subjects. Regions of interest were placed at the bilateral lungs and the whole body, and pulmonary accumulation was calculated. Results: All the control subjects demonstrated more than 90% of radioactivity in the lungs until 20 min. In contrast, all the patients showed values less than 80% at 5 min. In the cirrhosis patients with hypoxemia, the presence of intrapulmonary shunt was confirmed on quantitative lung perfusion scan. In control subjects, pulmonary accumulation of Tc-99m MAA dropped as a function of time and became less than 90% after 30 min. Conclusion: The timing of measurements is essential in evaluating intrapulmonary shunt.

Brain perfusion SPECT (BP-SPECT) has characteristic patterns of abnormality, enabling the differential diagnosis of dementia. The purpose of this study was to measure interobserver variations in the diagnosis of dementia using BP-SPECT. BP-SPECT images of 57 cases, 19 of Alzheimer's disease (AD), eight of multi-infarct dementia (MID), three of Pick's disease, five of other dementias, and 22 normal controls, were interpreted by ten nuclear medicine physicians with varying levels of experience. Brain MR images of the cases were then interpreted apart from SPECT. The physicians independently rated all of the diagnoses listed beforehand according to a five-point scale, with clinical information provided. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (Az) were calculated. Az varied from 0.48 to 0.87. Mean Az's were significantly larger (p< 0.05) in the diagnosis by SPECT than in that by MRI (0.715 and 0.629 for dementia vs. normal, 0.670 and 0.560 for AD or MID vs. normal, 0. 610 and 0.416 for AD vs. normal, and 0.672 and 0.412 for AD vs. MID, respectively). Considerable interobserver variation was present in BP-SPECT interpretation. BP-SPECT may be more effective for the evaluation of dementia than MRI when the same nuclear medicine physicians interpret both images.

Mucosa-associated lymphoid tissue (MALT) lymphoma has been established as a distinct entity among non-Hodgkin's lymphomas, and the most common primary site is the stomach. We describe scintigraphic findings in a patient with MALT lymphoma. of the thyroid. A 71-year-old woman with Hashimoto's thyroiditis suffered from rapid cervical swelling, and ultrasonography and CT revealed a thyroid nodule. The nodule showed accumulation of Tc-99m pertechnetate comparable to the surrounding thyroid tissue, mimicking a benign nodule. Both Ga-67 and Tl-201 imaging visualized the lesion as an increased uptake area. After radiotherapy, abnormally increased uptake disappeared on 67Ga images, which predicted a favorable outcome. MALT lymphoma of the thyroid may be visualized as a warm nodule on Tc-99m pertechnetate scintigraphy.

Background: The effect of different insufflation pressures and durations of CO2 pneumoperitoneum on the growth of liver metastasis was investigated in a mouse model. The possible mechanisms involved in the pressure-related enhancement of liver metastasis were also examined. Methods: Mice inoculated intraportally with colon 26 cells underwent CO, pneumoperitoneum at different pressures (5, 10, or 15 mmHg) for 30 or 60 min, or received no treatment other than tumor cell inoculation (control). The subsequent growth of liver mestastases was examined. Mice injected intraportally with In-111-oxine-labeled colon 26 cells underwent pneumoperitoneum at three different pressures or served as controls. The radioacitivity of the liver was determined to evaluate tumor accumulation in the liver. Mice received pneumoperitoneum at three different pressures or received trocar placement alone. Changes in plasma interleukin-6 levels were determined. Results: The growth of liver metastases on day 14 was influenced by increased insufflation pressures (p<0.05) rather than the prolonged duration of pneumoperitoneum without significant interaction. The 15-mmHg pneumoperitoneum group showed a higher (p<0.05) accumulation of radioactivity in the liver compared with the 5-mmHg pneumoperitoneum group and controls. Pneumoperitoneum groups with 5 and 10 mmHg showed higher (p<0.05) peak levels of IL-6 compared with controls. Conclusions: An elevated insufflation pressure plays an important role in the enhancement of liver metastases, and this pressure-related adverse effect may be partly relevant to facilitating accumulation of tumor cells in the liver.

The purpose of this prospective study was to detect symptomatic cerebral vasospasm in aneurysmal subarachnoid haemorrhage (SAH) by a non-invasive mean cerebral blood flow (mCBF) quantification using Tc-99m-ethyl cysteinate dimer. Measurement of mCBF without blood sampling and single photon emission tomography (SPECT) were performed at 1 and 7 days after surgery in 35 consecutive SAH patients, of whom 16 were examined at day 30 as well. A decrease in mCBF of more than 10% on day 7 versus day 1 was considered to indicate vasospasm. On visual interpretation of SPECT, a perfusion decrease which appeared newly on day 7 was considered to indicate vasospasm. In total, nine of 35 patients had cerebral vasospasm confirmed by computed tomography (CT) and/or angiography. The mCBF measurement showed a 77.8% (7/9) sensitivity, a 88.5% (23/26) specificity, a 70.0% (7/10) positive predictive value, and a 92.0% (23/25) negative predictive value. SPECT yielded a 33.3% (3/9) sensitivity, a 73.1% (19/26) specificity, a 30.0% (3/10) positive predictive value, and a 76.0% (19/25) negative predictive value. On SPECT, decreased perfusion was observed in most of the patients at clipping sites, which might represent post-operative transient abnormal perfusion and should not be read as vasospasm. In conclusion, thus mCBF measurement is more accurate than visual interpretation of SPECT for detecting vasospasm. ((C) 2002 Lippincott Williams & Wilkins).

近年, 癌治療においてQuality of Life (QOL) の向上が重要な課題となっている. 放射線治療におけるQOL評価法はいまだ確立された方法がなく, また放射線治療が患者のQOLに与える影響も明らかにされていない. そこでわれわれはQOL調査票を用いて, 放射線治療が施行された患者のQOLの変化を調べ, QOLに及ぼす影響についた考察した. QOL調査票は厚生省粟原斑のrがん薬物療法におけるQOL調査票を使用した. 355例の成人癌患者を対象とし, QOL調査は治療開始時・中・終了時の3回行い評価した. 症例全体ではQOLスコアは治療終了時に改善が認められた. これは高齢者においても岡様の結果であった. また婦症照射例 (その多くがPS2-4) でQOLスコアの改善が顕著であった. 化学療法供用例や口腔内が照射された例ではむしろQOLスコアの悪化が見られた. 以上より放射線治療は高齢者やPS不良群でもQOLを損なわず治療可能であり, また姑息・対症照射鋼でQOLの改善が明らかであった. ただし化学療法併用群や口腔内が照射される例では, 注意深く治療する必要がある. 本調査票は放射線治療患者のQOL評価に有用である.

In this report, we examine the case of a 6-year-old girl with a mixed oligodendroglioma demonstrating uncommon neuroradiological images. CT and MR showed an intratemporal mass with multilocular cystic formation and intratumoral massive calcification, suggestive either of astrocytoma, dysembryoplastic neuroepithelial tumor, or ganglioglioma as a presumptive differential diagnosis. The tumor was almost completely removed. Post-operative histological examination revealed a mixed oligodendroglioma with a small component of astrocytoma. The combination of radiotherapy and chemical treatment was supplemented. Copyright © 2001 Elsevier Science Ltd.

We have evaluated the potential of Re-188-labeled monoclonal antibodies (MAbs) modified with 2-iminothiolane (2IT) for targeting small-cell lung cancer (SCLC). Radiolabeled MAbs NK1NBL1 and C218 recognizing neural cell adhesion molecule were injected i.v. into athymic mice inoculated with human SCLC tumors, and the biodistribution was examined. NK1NBL1 localized in the tumors better than C218. Re-188-labeled MAbs cleared from the blood faster than I-125-labeled counterparts, resulting in higher tumor-to-blood ratios. In conclusion, the Re-188-labeled MAbs are attractive candidates for imaging and therapy of SCLC.

The "affinity enhancement system," a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody. Methods: Antineural cell adhesion molecule/antihistamine bispecific antibody NK1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NCI-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later I-125-labeled bivalent histamine hapten. I-125-labeled intact NK1NBL1 was injected into other groups of mice. Biodistributions were examined as a function of time. Results: In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7, respectively, at 5 h, whereas I-125-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrated clear tumor-to-normal tissue contrast. Dosimetry showed that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1. Conclusion: This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer.

塩酸コルホルシン ダロパートは，フォルスコリンの水溶性誘導体研究から見出された生薬由来の急性心不全治療薬である．本剤はフォルスコリンと同様に，β受容体を介さずにcAMPの合成酵素であるアデニル酸シクラーゼを直接活性化し，細胞内のcAMP濃度を高めることにより薬理作用を発現する．本剤は水溶性，作用の持続時間，血液脳関門透過性，経口活性およびアデニル酸シクラーゼのサブタイプ選択性などの点でフォルスコリンとは異なる．本剤は，陽性変力作用と血管拡張作用を示すイノダイレーター(inodilator)である．本剤の陽性変力作用は，β刺激薬やPDE阻害薬の作用が減弱するβ受容体脱感作モデルでも保持された．また，本剤は各種実験的心不全モデルに対し改善作用を示した．臨床試験においても，本剤は心不全患者の血行動態を改善し，同時に自覚症状や身体所見の改善も認められた．さらに，カテコラミン抵抗性の心不全患者でも有効であった．本剤は，世界初のアデニル酸シクラーゼ賦活薬製剤である．今後市販後調査(PMS)の中で，さらにその有効性，安全性および品質などに関して情報収集し，より適正な使用法を確立していく必要がある．本剤の臨床的位置付けがさらに明確になり，急性心不全の治療薬として一翼を担うことができれば幸いである．

The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and I-125-labeled DTPA-indium dimer hapten (I-125-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer. Methods: Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, I-125-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')(2) fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of I-125-di-DTPA-In hapten or I-125-labeled F6 F(ab'),. Results: In mice injected with BsMAb F6-734 and I-125-di-DTPA-In hapten, tumor uptake was 9.1% +/- 2.1%, 8.7% +/- 3.5%, 8.0% +/- 2.3%, 5.1% +/- 0.9% and 3.5% +/- 1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0 +/- 12.5, 32.3 +/- 10.9 and 10.4 +/- 2.7 at 24 hr. Iodine-125-F6 F(ab')(2) fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8 +/- 0.6, 7.3 +/- 2.9 and 3.6 +/- 1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast. Conclusion: This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.

Imaging and therapy using radiolabeled monoclonal antibodies have proved useful in many clinical studies. However, immunogenicity of mouse antibodies to human and insufficient tumor-to-normal tissue ratios remained to be solved. Chimerization and humanization by genetic engineering, and multistep targeting techniques have enabled lower immunogenicity and higher tumor-to-normal tissue contrast. Peptides like somatostatin-analogs have been reportedly useful in imaging tumors, which are either somatostatin receptor positive or negative. Elevated normal tissue accumulation of radiolabeled peptides is a drawback in aiming internal radiation therapy.

In order to evaluate the feasibility of 188Re-labeled antibodies for radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on the surface membranes of colorectal cancer cells, was directly labeled with 188Re, obtained from a 188W/188Re generator, using stannous tartrate and compared with 125I-labeled B72.3. As a control, a human IgG was also radiolabeled with 188Re and 125I. Prepared antibodies for 188Re labeling could be stored as kits. Biodistribution was determined in nude mice inoculated with human colorectal carcinoma LoVo. Labeling efficiency and immunoreactivity of 188Re-B72.3 were 80.3% and 64.7%, respectively. 188Re-B72.3 localized specifically in the LoVo tumors. Although the absolute tumor accumulation level of 188Re-B72.3 was lower than 125-B72.3, 188Re-B72.3 demonstrated higher tumor-to-blood contrast than the 125I-labeled counterpart, 2.04 ± 0.44 vs. 1.05 ± 0.28 at 96 hours, because of fast clearance from the blood. 188Re-B72.3 seemed efficient for the imaging and therapy of colorectal carcinoma.

The use of three phase Tc-99(m) (V)DMSA scintigraphy is reported in a patient with Paget's disease of bone before and after intravenous pamidronate therapy. It was a useful modality for estimating the activity of Pagetoid lesions and the therapeutic effect of pamidronate, from a different aspect to bone scintigraphy. Three phase Tc-99(m) (V)DMSA scintigraphy evaluates both the blood flow and the metabolic activity of Pagetoid bone.

Objective. To-investigate the septum-like structures in predominantly lipomatous tumors, by correlating fat-suppressed MR images with histopathologic findings. Design and patients. The MR findings of three cases of well-differentiated liposarcoma (atypical lipoma), one case of lipoma-like component of dedifferentiated liposarcoma. and nine cases of lipoma were analyzed. T1-, T2-, and fat-suppressed T1- weighted images after Gd-DTPA administration were obtained. Surgical specimens from five patients (four with liposarcoma and one with lipoma) were also scanned with a MR unit, and compared with the pathologic findings. Results and conclusions. Enhancement features of lipoma and liposarcoma were well visualized on fat-suppressed T1-weighted images after Gd-DTPA administration. The septum-like structures of liposarcoma are thick and enhanced considerably, while septa of lipoma are thin and enhanced only slightly. Pathologically, the septum-like structures of Liposarcoma contained muscle fibers and the septa of lipoma represented fibrous capsule, Identification of well-enhanced septa in a predominantly lipomatous tumor helps to differentiate malignant tumors horn lipomas. As the septum-like structures of liposarcoma contain a skeletal muscle component the tumor might need more extensive surgical procedures including resection of adjacent muscles.

Two cases of pigmented villonodular synovitis of the ankle were reported. One lesion showed low-intensity on both T1- and T2-weighted images as shown in the previous literature, but the other lesion containing much less hemosiderin on histologic findings, showed the unusual high-intensity on T2-weighted MR images.

To determine whether extraabdominal desmoid can be correctly diagnosed using both magnetic resonance imaging (MRI) and scintigraphy with pentavalent technetium-99m dimercaptosuccinic acid and gallium-67 citrate, MRI (T1- and T2-weighted images) and scintigraphy were performed in 18 patients with 27 histologically proved extraabdominal desmoid tumors. The extraabdominal desmoid tumors were characterized by positive uptake of pentavalent technetium-99m dimercaptosuccinic acid and lack of uptake of gallium-67 citrate on scintigraphy. These tumors were isointense to skeletal muscle on T1-weighted MRIs and hyperintense on T2-weighted images. They also displayed septum-like internal inhomogeneity and surrounding hypointense capsular band. The combination of scintigraphy and MRI is of value in correctly diagnosing extraabdominal desmoid tumors except in the rare case of fibrotic very low-grade sarcoma. (C) Elsevier Science Inc., 1997.

We examined the potential of radiolabeled somatostatin analogs, I-125-Tyr-3-octreotide (I-125-octreotide), In-111-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (In-111-octreotide), and Re-188-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model, Tyr-3-octreotide was labeled with I-125 by the chloramine T method, and In-111-octreotide was obtained as a kit, while Re-188 was eluted from a W-188/Re-188 generator, and octreotide was directly labeled with Re-188 by reducing disulfide bonds. The I-125-, In-111- and Re-188-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5 +/- 0.2, 0.3 +/- 0.1, 0.3 +/- 0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for I-125-, In-111-, and Re-188-octreotides, respectively. Accumulations of In-111-octreotide in normal tissues were lower than those of I-125- and Re-188-octreotides. Re-188-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, In-111-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.

The murine monoclonal antibody (mAb) 145-9 recognizes an epitope present on CA125 but different from the epitope defined by the mAb OC125. To evaluate the clinical usefulness of the 145-9 antibody, immunoscintigraphy was performed in ovarian cancer patients and the effect of circulating CA125 on tumor imaging was investigated. Two milligrams (74 MBq) of In-111-labeled 145-9 was injected intravenously into 11 patients with ovarian cancer. Pre-injection serum CA125 concentrations were between 166 U/ml and 7414 U/ml. Tumors were visualized in 10 of 11 patients. In two patients, lymph nodes that were not detected by other imaging modalities but were clinically suspected as metastases were visualized. There was no correlation between serum CA125 level and antibody uptake in the tumors. Immune complexes between the antibody and circulating antigen were observed in sera of all the patients, but the fraction of radioactivity in complex form did not correlate well with serum CA125 levels. The immune complexes survived in the circulation and the circulating radiolabel, including immune complexes, was still bound to solid-phase CA125. The plasma clearance rate and hepatic uptake of the antibody were not significantly affected by circulating CA125. In conclusion, the antibody 145-9 formed complexes with CA125 in vivo but this did not compromise the outcome of antibody imaging. The antibody 145-9 can be used in immunoscintigraphy of ovarian cancer irrespective of serum CA125 level.

Radiographic, computed tomographic and scintigraphic findings of a patient with separated, multilocular periosteal ganglion are reported. Multiple periosteal cystic masses with calcification in small parts of the cyst walls were demonstrated in the surface of the left tibia by plain radiograms and CT. The accumulations of technetium-99m hydroxymethylene diphosphonate and pentavalent technetium-99m dimercaptosuccinic acid were shown in the calcification in the periosteum and wall of the cyst. Needle puncture revealed that the masses were filled with jelly-like fluid. The masses were diagnosed as multiple ganglionic cysts at the periosteum of the left tibia.

A specific gas chromatography/mass spectroscopy method with a detection limit of 0.1 ng/mL was developed for the measurement of 6-(3- dimethylaminopropionyl)forskolin (1) in beagle plasma. Using this method, plasma concentrations of 1 in beagles given pharmacologically effective intravenous doses of 1-HCl were determined. The observed maximal plasma concentrations rapidly decreased with time, and half-lives of the α-phases were < 9 min. Pharmacological effects of 1 on the cardiovascular parameters were simultaneously evaluated in one of the studies. Decreases of the pharmacological effects were slower than decreases in plasma concentration of 1. In addition, 6-(3-methylaminopropionyl)forskolin (N-monodemethyl 1), an expected initial metabolite of 1, was prepared and found to be as pharmacologically active as 1 in beagles. These results and others strongly suggest that a metabolite(s) of 1 contributes to the pharmacological effects of 1 in beagles.

Effects of prolonged noradrenaline infusion on the density of cardiac β adrenoceptors, phosphodiesterase (PDE) and adenylate cyclase (AC) activities, and the ability of NKH477, 6-(3-dimethylaminopropionyl) forskolin hydrochloride, to increase tension development and heart rate were studied in rat cardiac preparations. Noradrenaline infusion (400 μg/kg/hr, s.c.) for 7 days significantly decreased cardiac β-adrenoceptor density (B(max)), whereas the binding affinity (Kd) of the ligand was unchanged. The basal cardiac PDE activity was increased in treated rats, whereas there was no difference in the basal cardiac AC activity between treated and untreated rats. Significant decreases in basal developed tension and heart rate were observed in the left and right atrial muscles from treated rats, respectively. The positive inotropic and chronotropic potencies of NKH477 were unaffected by noradrenaline infusion, whereas the positive inotropic potencies of isoproterenol and 3-isobutyl-1-methylxanthine were significantly reduced. Thus, NKH477 appears to be superior to β-adrenoceptor agonists or PDE inhibitors as a cardiotonic drug in the treatment of heart failure accompanied by β-adrenoceptor downregulation.

Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered I-125- and In-111-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using In-111-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL.

We report pre- and post-operative three-dimensional (3D)-spiral CT images in a patient with multiple exostoses, Images of 3D-CT, which were performed using the integrated 3D software of the CT system, showed the exact shapes and locations of the individual tumors around the knee joint in comparison with the surgical findings and resected specimen, 3D-spiral CT images of multiple exostoses would be useful for the planning of surgical procedure. (C) 1996 Elsevier Science Ltd.

A murine monoclonal antibody MLS102 recognizes sialosyl-Tn antigen in mucin and immunohistochemically reacts with more than 80% of colorectal cancer tissues, The purpose of this study was to assess the usefulness of this monoclonal antibody for the immunoscintigraphy of colorectal cancer. Planar and SPECT images were obtained on day 2 or day 3 after injection of 2 mg and 74 MBq In-111-labeled MLS102 antibody into 17 patients with colorectal cancer. Nine of 11 primary tumors and 4 of 6 locally recurrent tumors were detected. Positive images were obtained in all tumors larger than 4.5 x 2.7 cm. Three tumors of less than 2.5 cm and 1 recurrent tumor, which was missed by other imaging modalities, were negative. There were no adverse reactions. Human anti-(mouse Ig) antibody developed in 4 patients. Although improvement of detectability for smaller tumors needs to be pursued, the antibody MLS102 is potentially promising for use in immunoscintigraphy of colorectal cancer.

Objective: The purpose of this study is to investigate the CT and MR findings of muscular involvement by malignant lymphoma and identify the CT acid MR features that may assist in their diagnosis. Materials and Methods: Magnetic resonance imaging was performed on four patients (five lesions) with pathologically proven non-Hodgkin lymphoma using a 1.5 T unit (Cases 1, 2, and 4) and a 0.5 T scanner (Case 3). Computed tomography scans were carried out on three patients (Cases 1, 3, and 4). Results: The lesions that extended along muscle fascicles with preserved fat planes looking like swelling of the muscle were of slightly hyper- to isointensity relative to uninvolved muscles on T1-weighted images, of hyperintensity on T2-weighted images, and of low or isodensity on CT. Microscopically, lymphoma cells were seen clustering among normal and atrophic muscle fibers in a biopsy specimen of one patient. The lesions enhanced relatively homogeneously after Gd-DTPA injection. In three cases, vessels were coursing through the lesion on MRI and in two cases on enhanced CT. Conclusion: Magnetic resonance imaging proved useful to show the extension of involvement of muscular lymphoma compared with CT. The diagnosis of infiltration of muscle by lymphoma is entertained when a lesion of relatively homogeneous intensity and density extends along the muscle fascisles without obliteration of the fat planes and especially when vessels are identified within the lesion.

Technetium-99m (V) DMSA scintigraphy was performed in 17 patients with 37 chondrogenic tumors (13 osteochondromas, 14 enchondromas, and 10 chondrosarcomas) that had previously shown uptake of Tc-99m HMDP. Technetium-99m (V) DMSA showed high uptake by all chondrosarcomas, but low or no uptake always indicated benign chondrogenic tumors. Technetium-99m (V) DMSA scintigraphy may be superior to Tc-99m HMDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, and could also be useful for diagnosing the malignant transformation of chondrogenic tumors.

The authors reported computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphic findings of a patient with solitary muscular tuberculosis in the forearm. All these findings resembled those of other granulomatous inflammatory lesions in the soft tissue such as muscular sarcoidosis.

To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected In-111-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3 +/- 9.4 and 10.0 +/- 3.6 % injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1 +/- 2.5 and 3.7 +/- 0.9 %ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) alpha chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with I-125-labeled anti-Tac MoAb (22.5 +/- 6.9 and 22.8 +/- 9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with I-125-labeled RPC5 MoAb (12.0 +/- 5.1 and 7.5 +/- 4.6 %ID/g, respectively). Similar results were obtained with In-111-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb.

Injection of avidin can decrease the background radioactivity due to a radiolabeled biotinylated monoclonal antibody. We compared the chase effects of avidin, streptavidin, neutravidin, and avidin-conjugated ferritin on a radiolabeled antitumor monoclonal antibody in tumor-bearing nude mice, A radioiodine-labeled biotinylated monoclonal antibody (OST7) was administered to athymic mice bearing osteogenic sarcomas. After 24 h, an avidin, streptavidin, neutravidin or avidin-conjugated ferritin chaser was intravenously injected into the mice. At 2 h after the chase, the biodistribution of the radiolabeled monoclonal antibody was determined. Clearance from the blood was dose-dependently accelerated by avidin and its effect was 10-fold stronger than that of neutravidin or avidin-ferritin. Streptavidin did not promote clearance of the biotinylated antibody, Avidin was the most effective chasing agent for improving the biodistribution of the radiolabeled biotinylated monoclonal antibody among the four avidin derivatives tested.

The bronchodilator and cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride) were evaluated. In anesthetized guinea pigs, i.v. bolus injections of NKH477 (1–100 µg/kg) inhibited the bronchoconstriction induced by inhaled leukotriene D4, increased the heart rate (HR) and decreased the diastolic arterial blood pressure (DBP) in a dose-dependent manner. The bronchodilator effect of NKH477 was 1500 times more potent than that of aminophylline and 17 times less potent than that of isoproterenol. The selectivity of NKH477 for bronchodilation vs an increase in HR was 15 times higher than that of isoproterenol and similar to that of aminophylline and vs a decrease in DBP, the selectivity was 4 times higher than that of aminophylline and similar to that of isoproterenol. I.v. infusion of NKH477 (0.1–3 µg/kg/min) for 2 hr dose-dependently inhibited the bronchoconstriction induced by i.v. histamine. Isoproterenol (0.1 µg/kg/min, i.v.) enhanced the bronchoconstriction after termination of the infusion, whereas NKH477 did not. In conscious guinea pigs, inhalation of NKH477 (0.1–5 mg/ml) concentrationdependently inhibited the bronchoconstriction induced by inhaled histamine, and a high concentration of NKH477 (35.4 mg/ml) increased the HR. The bronchodilator effect of inhaled NKH477 was 15 times less potent than that of isoproterenol. The selectivity of inhaled NKH477 was similar to that of isoproterenol. These results indicate that NKH477 may be useful as a bronchodilator. © 1995, The Japanese Pharmacological Society. All rights reserved.

To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 μg/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 μg/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia. © 1995.

To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using In-111-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 mu g/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 mu g/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia.

The scintigraphic findings of a patient with pigmented villonodular synovitis are described and compared with the computed tomography and magnetic resonance imaging data. Intense uptake of pentavalent technetium-99m dimercaptosuccinic acid without gallium-67 citrate uptake indicates that pigmented villonodular synovitis has the features of a hyperplastic or neoplastic lesion rather than an inflammatory lesion from the point of view of nuclear medicine.

The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a ''chase'' avidin injection. Methods: A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with I-125, I-131 or Tc-99m. Radiolabeled biotinylated OST7 (10 mu g) was administered intravenously into nude mice bearing human osteosarcomas and 30 mu g of avidin was injected intravenously 6 or 24 hr later. Results: Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of I-125-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. Conclusions: This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as Tc-99m and I-123.

We report a case of histologically proven intraosseous hemangiomatosis in which marked accumulation of pentavalent technetium-99m-dimercaptosuccinic acid (Tc-99m(V)DMSA) and technetium-99m-hydroxymethylene diphosphonate (Tc-99m-HMDP) was observed in the osteolytic hemangiomatous lesions.

The diagnostic value of MRI and scintigraphy was studied in patients with Schwannomas of the upper or lower extremities. MRI (T1- and T2-weighted imaging), pentavalent Tc-99m-dimercaptosuccinic acid and Ga-67-citrate scintigraphy were performed in 11 patients with 12 histologically proven benign Schwannomas. All six tumors with a maximum diameter greater than or equal to 3 cm showed marked accumulation of pentavalent Tc-99m-dimercaptosuccinic acid, whereas they showed no uptake of Ga-67-citrate. MRI detected all of the tumors, and the lesions had a signal intensity equal to or slightly less than that of skeletal muscle on T1-weighted images and hyperintense to that of subcutaneous fat on T2-weighted images. MRI was superior to detect small Schwannomas of the extremities. A positive Tc-99m-dimercaptosuccinic acid scan and a negative Ga-67-citrate scan however is useful to distinguish sarcoma with myxoid change from Schwannoma.

131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before131I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 weekto 1 month after131I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from131I-MIBG therapy. Thus,131I-MIBG appears to be useful for the palliation of malignant pheochromocytoma. © 1994 Springer-Verlag.

Radiolabeled GA-17, a murine monoclonal antibody that reacts specifically with glioma cells, bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in vivo. The affinity constant of GA-17 F(ab')(2) fragment binding to NCI-H69 was 1.02x10(8)/M while that to the glioma cell line U87MG was 1.22x10(8)/M. Iodine-l25-labeled GA-17 F(ab')(2) fragments injected i.v. localized well in NCI-H69 cells xenografted in nude mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87+/-1.34%g(-1) (mean+/-SD, n=5) 24 h after injection. On the other hand, control monoclonal F(ab')(2) fragments accumulated in the xenografted tumor at 0.75+/-0.30%g(-1). The tumor-to-blood ratio was 1.8 for NCI-H69, while that of control F(ab')(2) was 0.60. In conclusion, the radiolabeled GA-17 F(ab')(2) fragment is expected to be useful clinically to visualize the small-cell lung cancer and in radioimmunotherapy.

The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an epitope designated as CA130 on the molecule expressing the OC125 epitope. Similarity of M11 epitope to the epitope of anti-CA130 antibodies and dissociation of antigen levels measured by the original CA125 assay and new CA125II assay were examined. Anti-CA130 antibodies partially competed with M11 for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in whom the serum CA125 concentration measured by the CA125II assay was different from that measured by the original assay. In 11 out of 12 patients the CA125 concentration was moderately or extremely high by the original assay but very low by the CA125II assay. Eight of the 11 patients had benign disease, one had no apparent disease and two had cancer. The antigen level determined by CA130 assay was very low in all the 11 patients. In one patient the CA125II assay showed a higher antigen level than the original assay or CA130 assay. The heterogeneity of the epitope expression could cause the dissociation of CA125 levels measured by the different monoclonal antibodies. (C) 1994 Academic Press, Inc.

This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells. Methods: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of I-125- and In-111-NE150 and the serial changes of the biodistribution were determined. Furthermore, athymic mice bearing NCI-H69 were either sham-treated or treated by a single hyperthermia at 42 degrees C or 43 degrees C for 1 hr, with the tumor-bearing leg in a water bath using pentobarbital anesthesia. Immediately after heating, the mice were given an intravenous injection of radiolabeled NE150, and the biodistribution was examined at 24 and 48 hr. Results: NE150 localized well in the transplanted tumor when compared with a control Mab. In mice treated at 43 degrees C, there was a 1.34- to 1.67-fold increase in the tumor uptake of I-125- and In-111-NE150 compared to sham-treated mice at both 24 and 48 hr. In addition, a 1.84- to 2.22-fold increase of the tumor-to-blood ratio was demonstrated, since radiolabeled NE150 cleared faster from the circulation in the mice given hyperthermia. A histological study demonstrated the infiltration of neutrophils in the perivascular spaces, indicating an increase of tumor vascular permeability, which might be one of the main reasons for the enhancement of Mab uptake. Conclusion: Hyperthermia seems to be a potential method of achieving an increased tumor accumulation of Mab in the radioimmunotargeting of SCLC.

Human small-cell lung cancer (SCLC) is considered a feasible target for immunotherapy using a radiolabeled monoclonal antibody (Mab). A murine Mab, NE150 (IgG1), reacts with the neural cell adhesion molecule, which is identical to cluster 1 antigen of SCLC. Methods: To estimate their therapeutic effects, NE150 and an isotype-matched control Mab were labeled with I-131 and administered intravenously as a single dose into athymic mice inoculated with a NCI-H69 SCLC xenograft. The absorbed dose in organs was also examined based upon a long-term biodistribution study of I-131-NE150. Results: Tumors (initial volume 563.4 +/- 223.5 mm(3)) treated with 11.1 MBq (300 mu Ci) of I-131-NE150 diminished and became invisible at days 30-33, demonstrating a 60-day mean growth delay to reach a tripled initial volume compared with sham-treated tumors. Cumulative absorbed doses were estimated to be 2310, 410, 500, 330, and 790 cGy for the tumor, liver, kidney, spleen and lung, respectively. Conclusion: Iodine-131-NE150 had potent therapeutic effects against SCLC transplants in athymic mice, however, careful assessment of the side effects, improvement of radioiodination and chimerization of the Mab might be necessary to achieve efficient targeting in clinical therapeutic applications.

The authors report marked accumulation of pentavalent technetium-99m dimercaptosuccinic acid in metastatic tumors from a renal cell carcinoma in the brain and the scalp on brain SPECT images.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester bond using a new metabolizable MESS linker, N-[[4-(maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS-OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as 67Ga-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-non-target ratio of radioactivity by MoAbs. © 1994.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A Ga-67 chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG(1)) through an ester bond using a new metabolizable MESS linker, N-[[4-(maleimidoethoxy)succinyl]oxy]succinimide (Ga-67-DFO-MESS-OST7). When injected into normal mice, Ga-67-DFOMESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with Ga-67-DFO-EMCS-OST7, which was prepared under identical conditions to Ga-67-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release (GaSDF)-Ga-67. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of Ga-67-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the Ga-67-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of Ga-67-SDF. In athymic mice bearing osteogenic sarcoma, Ga-67-DFOMESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with Ga-67-DFO-EMCS-OST7. These results indicated that Ga-67-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as Ga-67-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-nontarget ratio of radioactivity by MoAbs.

PURPOSE: to assess the potential of technetium-99m (V) dimercaptosuccinic acid (DMSA) scintigraphy for diagnosis of soft-tissue tumors. MATERIALS AND METHODS: Tc-99m (V) DMSA scintigraphy was performed in 76 patients with histologic proof of soft-tissue tumors. In 57 of these patients, gallium-67 citrate scintigraphy was performed within 2 weeks after Tc-99m (V) DMSA scin-tigraphy. RESULTS: Uptake of Tc-99m (V) DMSA was clearly detected in almost all sarcomas, metastatic carcinomas, highly recurrent benign tumors (ie, extraabdominal desmoids and teno-synovial giant cell tumors), superficial and deep hemangiomas, and granulomatous soft-tissue lesions but was not found in other benign solid tumors of soft tissue. Uptake of Ga-67 citrate was clearly detected in all inflammatory lesions and metastatic carcinomas, eight of 14 sarcomas (57%), and two of 10 highly recurrent benign tumors (20%) but was not found in hemangiomas or benign soft-tissue tumors. CONCLUSION: Low-grade malignant and highly recurrent benign lesions, which often recur after surgery, were detected more accurately with Tc-99m (V) DMSA scintigraphy than with Ga-67 citrate scintigraphy.

The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the I-125-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. I-125-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti-CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule.

A murine monoclonal antibody 3H3 recognizes the basic fibroblast growth factor (FGF) and inhibits the growth of human glioblastoma cells both in vitro and in vivo. We studied the potential of a scintigraphic technique using the 3H3 antibody to detect tumors that produce basic FGF. I-125- and In-111-labeled 3H3 bound to U87MG human glioblastoma cells in vitro. U87MG cells were inoculated subcutaneously into nude mice. After development of the tumor, radiolabeled 3H3 was injected into the subcutaneous space surrounding the tumor. A high level of radioactivity from 3H3 was retained at the tumor, whereas an irrelevant antibody cleared rapidly from the injected site. Radiolabeled 3H3 was not retained in tumors that did not produce basic FGF. Scintigraphic detection of tumors expressing basic FGF would be valuable for the therapeutic application of the antibody.

Technetium-99m(V) dimercaptosuccinic acid (DMSA) and Ga-67-citrate scintigraphy were performed in three patients with primary and recurrent tenosynovial giant-cell tumor (one localized type and two diffuse type). In all cases, Tc-99m(V)DMSA showed marked accumulation in all primary and recurrent tumors; however, Ga-67-citrate showed no accumulation in any of the tumors. Technetium-99m(V)-DMSA scintigraphy was useful in detecting tenosynovial giant-cell tumor and in diagnosing recurrence of this tumor.

The effect of drugs on the release of CA125 antigen and the binding of anti-CA125 mono-clonal antibody (MoAb) to malignant cells was evaluated in vitro. TMCC-1, uterine cervical adenocarcinoma cells, were exposed to dexamethasone (DEX), sodium n-butyrate (NaB), dibutyryl cyclic AMP (dbcAMP), retinoic acid (RA), calcitriol (VD3), and interferon-γ (IFN-γ). NaB, RA and VD3 increased CA125 release per cell and125I-labeled anti-CA125 MoAb binding to the cells. DEX also increased the125I-labeled anti-CA125 MoAb binding to the cells, and CA125 antigen release per cell was also slightly increased. IFN-γ suppressed both CA125 release and125I-labeled MoAb binding. A combination of DEX, VD3 and RA and increased the binding of MoAb to TMCC-1 cells, but the amount of bound MoAb was not significantly different from that obtained by single drug treatment. DbcAMP had no significant effect on enhancing MoAb binding. Drugs can increase the binding of anti-CA125 MoAb to malignant cells and they may be applied to increase the tumor uptake of radiolabeled MoAbs in vivo. © 1993 Springer-Verlag.

Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA125, but the epitope it recognizes is different from that of monoclonal antibody OC 125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (gamma1) and light-chain (kappa) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with I-125, In-111 or Tc-99m demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the I-125-labeled or Tc-99m-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with I-131, In-111 or Tc-99m is promising for the radioimmunoimaging of ovarian cancer.

A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with Tc-99m without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, Tc-99m-labeled OST7 was cleared faster from the circulation than I-125-labeled OST7 or In-111-labeled OST7 in mice. Urinary and fecal excretion of Tc-99m were higher than those of I-125. When the I-125-labeled antibody was dual-labeled with Tc-99m, the blood clearance of Tc-99m was faster than that of I-125, suggesting release of Tc-99m from the antibody in vivo. Tc-99m-labeled OST7, however, gave a higher tumor-to-blood ratio than I-125- or In-111-labeled OST7 in mice bearing human osteogenic sarcoma. The Tc-99m-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability.

Technetium-99m(V)dimercaptosuccinic acid (DMSA) scintigraphy was performed in two patients with pathologically confirmed primary amyloidosis. Both patients had tumor-like deposits of AL-type amyloid in the abdomen. Marked uptake of the tracer by the amyloid deposits was noted. Technetium-99m-(V)DMSA scintigraphy appears to be useful in detecting the distribution of amyloid deposits and in determining the appropriate site for biopsy.

The human c-erbB-2 protooncogene product (erbB-2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB-2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2-61gamma and 6G10, recognize erbB-2 protein but bind to separate epitopes. SV2-61gamma was used as an immunoadsorbent and 6G10 as an I-125-labeled probe. A serum was considered positive for erbB-2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB-2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut-off value. These results suggest that circulating erbB-2 protein can be measured using the newly constructed IRMA. Since c-erbB-2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.

We evaluated 'BALL ELSA CYFRA21-1' kit, an immunoradiometric assay kit for cytokeratin 19. Monoclonal antibodies KS19-1 and BM19-21 are used for immunoadsorbent and indicator, respectively. There was no problems in reproducibility, dilution test and recovery test. Minimum detectable concentration was 0.42 ng/ml. The antigen measured by this kit was immunologically cross-reactive with tissue polypeptide antigen (TPA) and CYFRA21-1 concentration was closely correlated with TPA concentration in patient's serum. One of twenty-six healthy subjects showed serum concentration over a cut-off value of 2.0 ng/ml. Serum CYFRA21-1 concentration elevated in 5 of 10 esophageal cancer patients, 5 of 10 gastric cancer patients, 7 of 10 colorectal cancer patients and 6 of 10 pancreatic cancer patients. Positive rate in patients with benign disease including hepatopathy was low. BALL ELSA CYFRA21-1 kit is reliable and CYFRA21-1 could be a useful tumor marker in gastrointestinal cancer.

A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc-labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In-labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability. © 1993.

Background. CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. Methods. Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads. Results. The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated heads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. Conclusions. Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.

Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fe portion and or CH1 or CL region of murine IgG, and (2) human mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients.

The efficacy of NKH477, a novel water-soluble forskolin derivative, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital, propranolol or verapamil so that cardiac output had been reduced by about 40-50% of the respective control were all improved by NKH477 (10-100 μg) in a dose-dependent manner. With 100 μg NKH477, almost complete restoration of cardiac performance was attained in the respective cardiac failures. In the combination of NKH477 with ouabain (30 μg), 30 μg of NKH477 completely restored the cardiac function depressed by pentobarbital, associated with a slight but not significant increase in heart rate. No arrhythmias were induced by any of the NKH477 doses used in the experiments. These results suggest that NKH477 should be subjected to clinical trials in the treatment of cardiac failure. © 1992, The Japanese Pharmacological Society. All rights reserved.

CA125 is a high-molecular weight glycoprotein expressed on most serous-type ovarian cancer and some lung adenocarcinoma tissues. The effects of various drugs on the release of CA125 antigen into culture medium and on monoclonal antibody (MAb) binding to cancer cells were studied using 8 human cancer cell lines, all of which expressed CA125 on their cell surfaces. The effect of dexamethasone was seen at as low a concentration as 10(-9) m dexamethasone, and the release of CA125 and the binding of radiolabelled anti-CA125 antibody were completely inhibited after exposure to 10(-7) m dexamethasone. The number of antibody binding sites markedly decreased. In contrast, sodium butyrate increased CA125 expression. These findings were clearly detected in only 3 cancer cell lines and a significant effect was not seen in the 5 other cancer cell lines. Interferon-gamma, examined in 3 cell lines, suppressed in a dose-dependent manner in 2 CA125 expression cell lines, but enhanced it in one line. No apparent effects were seen after exposure to tissue necrosis factor or interleukin-2. These results suggest that drugs may regulate the CA125 antigen expression in some, but not all, cancer cells and may affect the biodistribution of radiolabelled MAbs.

Class-switched monoclonal antibody SV2-61r recognizes the extracellular domain of c-erbB-2 protooncogene products separate from the epidermal growth factor receptor. We studied the potential of SV2-61r for evaluating the amplification of c-erbB-1 protooncogene on cancer cells, which has been reported to have prognostic value in adenocarcinoma patients. Radiolabeled SV2-61r specifically bound to various adenocarcinoma cells in addition to c-erbB-1-transfected NIH-3T3 cells (A4) with the affinity constant of 4.4 X 10(8) M-1. SV2-61r injected i.v. localized well to A4 cells xenografted in nude mice. Tumor uptake and localization index of radioiodinated SV2-61r, probably due to the internalization and dehalogenation of formed antibody-antigen complexes. Biodistribution and specificity of targeting were assessed by comparison among three cells, A4, lung cancer SBC-3 (c=erbB-2 weakly positive) and B-lymphoblastoid Manca cells (c-erbB-2 negative). Tumor:blood ratios, obtained 48 h after injection, were 5.63, 1.45, and 0.68, respectively, indicating the potential of In-111-labeled SV2-61r for evaluating the amplification of c-erbB-2 protooncogene on cancer cells. Because of its close relationship with carcinogenesis and the uniform expression, c-erbB-2 protooncogene products seem to be the optimal target of imaging and therapy of adenocarcinoma patients.

In the multicenter clinical study of 111In-Antimyosin Fab (74 MBq, 0.5 mg), human anti-mouse antibody (HAMA) titers have been evaluated in serum from 456 patients using the sensitive enzyme-linked immunosorbent assay. Presence of HAMA was confirmed by the neutralization test or using the size exclusion high performance liquid chromatography (HPLC) analysis in 11 of 393 patients (2.8%). HAMA was still detectable in 2 patients even 40 weeks after injection. None of 7 patients judged as positive for the intradermal test, a patient with vascular pain or 3 patients with fever or flare and itching with fever, developed detectable levels HAMA in their serum. These results suggest that patients may develop HAMA response after infusion of 111In-Antimyosin Fab, but pathogenic role of HAMA in these patients remains to be studied.

The efficacy of MCI-154, a new pyridazinone cardiotonic agent, in improving heart failure was assessed in dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. MCI-154 in doses of 10–100 μg improved the cardiac function curve and restored it to the control level at 100 μg. At this dose, MCI-154 neither produced an increase in heart rate beyond the control value nor induced arrhythmias. The effects of MCI-154 were not affected by atenolol, a cardioselective β1-blocker. These results indicate that MCI-154 would be of potential use in the treatment of heart failure. © 1988, The Japanese Pharmacological Society. All rights reserved.

MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (I-100 nmol) was injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure. © 1987 Raven Press, Ltd., New York.

We compared the coronary vasodilator and cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. The drug was administered intraarterially. In SA node preparations MCI-176 reduced sinus rate and produced atrial standstill in large doses. In AV node preparations MCI-176 prolonged AV conduction time and produced second-or third-degree AV block in large doses only when administered into the artery supplying the AV node, but failed to affect AV conduction when administered into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations MCI-176 reduced the force of contraction. In spontaneously beating papillary muscles MCI-I76 failed to change the beating rate. MCI-176 increased blood flow in all preparations. The dose that doubled blood flow was slightly larger than the dose that produced a 15% increase in AV conduction time, but about one-third the dose that produced a 15% decrease in sinus rate. The dose estimated to reduce the force of contraction by half was more than 10 times the dose that doubled blood flow. The results indicate that MCI-176 can be classified as a nonvasoselective calcium antagonist but that it differs from others. © 1987 Raven Press, New York.

The effect of DHP-218, a dihydropyridine phosphonate Ca2+ channel blocker, on atrioventricular (AV) nodal conductivity was compared with its vascular effect in dogs. In isolated, blood-perfused AV node preparations, a long-lasting increase in AV conduction time which culminated in second- or third-degree AV block at large doses occurred when DHP-218 was injected into the AV node artery, but not when injected into the artery that supplies the His-Purkinje-ventricular system. However, with DHP-218, a far longer-lasting increase in blood flow through both arteries occurred, and at smaller doses it occurred with little effect on AV conduction. In anesthetized, open-chest dogs of which heart rate was controlled at 150 beats/min, intravenous DHP-218 produced an initially rather quick and later very slowly developing and long-lasting fall in blood pressure. AV conduction time was prolonged only after the largest dose. The functional refractory period of the AV conduction system was rather shortened in all doses examined except for the largest dose. A marked increase in AV conduction time which culminated in third-degree AV block was seen in one of six dogs, only under conditions in which the heart was deprived of central neural control. These results indicate appreciable selectivity of DHP-218 for vasculature versus the AV node. © 1987 Raven Press. Ltd., New York.

The effect of angiotensin II (Ang II) on prostaglandin (PG) production in dog renal and femoral vasculature was examined in vivo and in vitro. In pentobarbital anesthetized dogs, the reduction of blood flow induced by intraarterial infusion of Ang II was potentiated by pre-treatment with indomethacin (5 mg/kg) in the renal but not the femoral vasculature. Isolated renal and femoral arterial strips were incubated and the release of PGE2 and PGI2 (as 6-keto-PGF1α) into the medium was measured by radioimmunoassay. Basal PGE2 and PGI2 production by renal and femoral arterial strips was approximately the same. PGI2 production was predominant for both strips. Ang II stimulated PG production in renal but not femoral arteries. In the renal artery, Ang II-induced PG production was inhibited by indomethacin (10-6 M), mepacrine (10-4 M) and saralasin (10-6 M). These results suggest that Ang II stimulates PG production by the renal artery per se and the Ang II receptor is linked to phospholipase A2 in the renal but not the femoral artery. © 1984.

CT,MRI,PETの機能の相互比較を論じた

Digital Poster. Annual Meeting of Radiological Society of North America 2020. Virtual.

OP-423 European Journal of Nuclear Medicine and Molecular Imaging 2020;47 (Suppl 1): S212. DOI: 10.1007/s00259-020-04988-4

近畿大学附属病院における前立腺癌骨転移症例に対するSr-89治療の有効性と安全性について検討した。2008年1月から2011年10月までにSr-89を投与した患者は16例であり、評価可能な12例を対象とした。有効例は7例(58.3%)、不変例は4例(33.3%)、悪化例は1例(8.3%)であった。副作用として、Grade2の白血球減少が1例、ヘモグロビン減少が6例、血小板減少が2例認めたが、Grade3以上は認めなかった。有効例ではALP高値例が多く、Sr-89投与後に低下する傾向にあり、不変例・無効例のPSA値はSr-89投与後上昇する傾向にあった。(著者抄録)

FDG と F-MISO を用いたPET-CT が治療計画に有用であることを報告した。

Purpose:PET with 18F-misonidazole (F-MISO) is a non-invasive method of depicting tumor hypoxia. Result: Mean ± SD of SUVmax of the normal muscles was 1.26 ± 0.17. Based on these data, accumulation of F-MISO above a value of mean + 2SD (1.60 SUV) was regarded as indicating a hypoxic area. Except in one patient with postoperative recurrent uterine body cancer, the remaining five tumors showed a decrease in SUVmax or T/M ratio after approximately 20Gy of fractionated RT. Conclusions: Based on the SUVmax of the normal muscles, accumulation of F-MISO above 1.6 SUV was regarded as indicating a hypoxic area. Decrease in the SUVmax or T/M ratio, suggesting reoxygenation, was observed for most tumors after approximately 20Gy of fractionated RT. SUVmax of F-MISO before or during fractionated RT may predict the clinical outcomes of the tumors.

目的：F-MISOを利用し低酸素状態をPETによって画像化し、腫瘍内低酸素領域と再酸素化現象について検討する。 対象と方法：頭頸部癌、肺癌、食道癌、子宮体癌の合計6例を対象とした。腫瘍長径は28-68mmであった。検査はPET/CT装置を用い、全例治療前にFDG-PETを撮影した。F-MISOは体重1kg当たり約3.7MBq静脈投与し、約3時間後に撮影を行った。F-MISO-PETは、放射線治療前および約20Gy/10回の時期に原則2回行った。腫瘍周辺の正常筋肉へのF-MISOのSUVmaxの値は、95%信頼区間で1.15-1.49であった。これをもとに1.5 SUV以上のF-MISO腫瘍内集積を有意とした。さらに、腫瘍内のF-MISO SUVmaxを筋肉のSUVmaxで割った値(T/M 比)を求めた。 結果：放射線治療前のPETでは、6例全例で腫瘍内に1.5 SUV以上の集積を認めた。F-MISOの分布は、FDGの分布とは異なり腫瘍の一部に局在する傾向を認めた。2回撮影の行えた5例中4例では、照射に伴いT/M 比は低下した。 結語：F-MISO-PETで腫瘍内低酸素領域の画像化が可能である。分割照

機能画像を用いた放射線治療計画の現状と展望について述べた。（シンポジスト）

PET-CTシミュレーションのためのファントム実験の結果を報告した。

症例は73歳男性で、主訴は下痢。大動脈解離(DebakeyI型)術後1週間より発症。CTで解離の及んでいた下腸間膜動脈の閉塞を認め、虚血性腸炎と考えた。解離術後に発生する腸管虚血は稀な合併症で、上腸間膜動脈閉塞が原因となることが多く、下腸間膜動脈が原因となることは極めて稀（本邦１９８５～０３年の間で３例）である。虚血性腸炎発症時期は術後数週からという報告が多い。本症例でも術後1週間から発症しており、虚血性腸炎は解離術後から発症までにはタイムラグがあることを知っておくことは重要である。

腹部CTにて左腎腫瘍を指摘されて当院泌尿器科受診。腹部CTでは均一で骨格筋と同程度のCT値であり、内部に小さな石灰化がみられた。脂肪成分は指摘できず。造影CT早期相では均一によく造影されて、後期相では周囲の腎よりも低吸収であったがtime density curve 上は漸増性を示していた。MRI T2強調画像では骨格筋と同程度の低信号であり、chemical shift imageでは微少脂肪成分は指摘できず、in phase, opposed phaseとも腫瘤は腎実質よりも高信号を示していた。Dynamic studyではCT同様均一に造影されている。T2強調画像で腫瘍そのものが低信号を示しており、被膜の同定は不可能であった。脂肪成分が少ない血管筋脂肪腫との鑑別に苦慮したが、clear cell carcinoma以外の悪性腫瘍の可能性も考え、左腎摘出術を施行。Gerota筋膜表面の血管は強く怒張し、易出血性であった。左腎上極の癒着も著しかった。割面は灰白色で均一であった。組織診断はgranurlar cell carcinomaであった。

造影ＣＴにおけるショック、過敏症はアナフィラキシー様反応と認識され、治療、予防のためエピネフリン（商品名：ボスミン）投与が必須となっている。 副作用発現時のボスミン投与時期の明確な報告はなく、中等症以上の症例では症状発現後遅くとも１分以内の投与が推奨されている。また、気道確保等の救命措置が遅れがちなＣＴ室ではより早期段階での投与が望まれる。 以上の観点から、ボスミンの投与開始時点を検討した結果、副作用軽症例のうち、 発赤を伴った場合はアナフィラキシー様反応に特有（アナフィラキシー様症状時、８４％発現）と考え、これが認められた時点でエピネフリン筋注を開始する事とした。

造影ＣＴにおけるショック、過敏症はアナフィラキシー様反応と認識され、治療、予防のためエピネフリン（商品名：ボスミン）投与が必須となっている。 副作用発現時のボスミン投与時期の明確な報告はなく、中等症以上の症例では症状発現後遅くとも１分以内の投与が推奨されている。また、気道確保等の救命措置が遅れがちなＣＴ室ではより早期段階での投与が望まれる。 以上の観点から、ボスミンの投与開始時点を検討した結果、副作用軽症例のうち、 発赤を伴った場合はアナフィラキシー様反応に特有（アナフィラキシー様症状時、８４％発現）と考え、これが認められた時点でエピネフリン筋注を開始する事とした。

造影ＣＴにおけるショック、過敏症はアナフィラキシー様反応と認識され、治療、予防のためエピネフリン（商品名：ボスミン）投与が必須となっている。 副作用発現時のボスミン投与時期の明確な報告はなく、中等症以上の症例では症状発現後遅くとも１分以内の投与が推奨されている。また、気道確保等の救命措置が遅れがちなＣＴ室ではより早期段階での投与が望まれる。 以上の観点から、ボスミンの投与開始時点を検討した結果、副作用軽症例のうち、 発赤を伴った場合はアナフィラキシー様反応に特有（アナフィラキシー様症状時、８４％発現）と考え、これが認められた時点でエピネフリン筋注を開始する事とした。

3D-SRT(3-demensional stereotaxic ROI template)はSPMの標準化機能を利用し、あらかじめ決められた関心領域の局所脳血流を解析するソフトである。3D-SRTを用いてAlzheimer病の診断の制度、有効性を判別分析を用いて検討した。今回の結果では的中率は100％、誤判別率は5.39％との結果になり、臨床において診断に有用なツールであると思われた。

（目的）Tl-201心筋SPECTにおいて、QGS上の壁運動と壁厚の定量し、正常例における標準値を求めた。さらに、冠動脈造影にて冠動脈病変が確認された虚血性心疾患（IHD）患者のQGS壁運動と壁厚を求め、虚血心筋の診断における有用性について検討した。 （方法）対象は、心エコー、心電図、臨床経過によって、IHDを否定された10例を正常群（64±8歳）とした。IHD例は、冠動脈造影所見によってLAD群4例、RCA群8例、LCX群4例と群分けした。負荷・Tl-201投与直後（早期像）および3時間後（後期像）に、2検出器型ガンマカメラにより、180度収集、R-R間隔8分割により撮像した。 （結果）正常群の壁運動は、早期像と後期像の間で、心尖部、中隔、後下壁に有意差があった。正常群の壁厚は、早期像と後期像の間で、心尖部、中隔、後下壁、側壁に有意差があった。正常群とIHD群において、（後期像中隔壁運動を除く）いずれの領域にも壁運動と壁厚に有意差を認めた。また、正常群の標準値をもと

（目的）Tl-201心電図同期心筋SPECTにおいて、QGS上の壁運動と壁厚の定量し、正常例における標準値を求めた。さらに、冠動脈造影にて冠動脈病変が確認された虚血性心疾患（IHD）患者のQGS壁運動と壁厚を求め、虚血心筋の診断における有用性について検討した。（方法）対象は、Tl-201心筋SPECTを施行したが、心エコー、心電図、臨床経過によって、IHDを否定された10例を正常群（年齢64±8歳）とした。IHD例は、冠動脈造影所見によってLAD群4例、RCA群8例、LCX群4例と群分けした。負荷・Tl-201投与直後（早期像）および3時間後（後期像）に、2検出器型ガンマカメラにより、180度収集、R-R間隔8分割により撮像した。（結果）正常群の壁運動は、早期像と後期像の間で、心尖部（p=.0009）、中隔（p=.0018）、後下壁 （p=.0025）に有意差があった。正常群の壁厚は、早期像と後期像の間で、心尖部（p=.0001）、中隔（p=.0014）、後下壁（p=.0406）、側壁（p=.0356）に有意差があった。正常群とIHD群において、（

脳血流SPECT検査において、統計学的画像解析はその詳細な血流低下領域を描出するために必要な手法となっている。3D-SSPは統計学的画像解析の一つであるが、解析の過程でNormal Databaseが必要になり、より詳細な検討のためには厳密には検査機器ごとのDatabaseを作成する必要がある。当院で使用している機器であるADAC社製FORTEにおいて^99mTc-HMPAO SPECTのNorma Database作成を試みた。

Alzheimer型痴呆の画像診断は、SPMや3D-SSPなどの統計学的画像解析により大きく変化し、早期の血流低下も診断可能となってきた。しかし、これらの方法では血流量の低下を視覚的に判断するもので、数値による比較は動脈血採血など煩雑な手技や、独自のデータベースの構築を必要とする場合が多く、実施が難しい面がある。VOI classicはTalairach atlasのグリッドを用いて脳の領域を設定し、その領域に含まれるピクセル数により領域毎の平均値を算出するソフトウェアである。各領域の血流量を比較的変化の少ない小脳と比較することにより、簡便にAlzheimer型痴呆の診断が可能であるかどうかをVOI Classicを用いて検討した。

（目的）テクネシウム製剤を用いたQGS負荷心筋シンチは、虚血心筋のviability評価の有用性が確立されている。今回、タリウム201を用いたQGS壁運動が虚血心筋の評価に有用であることを示すため、QGS壁運動を定量的、三次元的に評価し、虚血性心疾患群の冠動脈別比較、検討を行った。（方法）対象は当院でタリウム負荷心筋シンチを施行した患者で、心エコー、心電図、臨床経過で虚血性心疾患が否定された10例を正常群とした。虚血性心疾患例は、冠動脈造影検査で有意な狭窄を認めた患者をLAD群4例、LCX群8例、RCA群4例に分類した。負荷・タリウム投与直後（早期像）、および3時間後（後期像）とし撮像した。QGS（Quantitative Gated SPECT）プログラムのBull’s eye 表示画像から心尖部、前壁、中隔、後下壁、側壁の5区域を設定し、区域ごとの壁運動量の平均値をそれぞれの区域の壁運動量とした。（結果）正常群の壁運動は、早期像と後期像の間で、心尖部、中隔、後下壁に壁運動の有意差が

Alzheimer型痴呆の画像診断は統計学的画像解析により大きく変化し、早期の血流低下も診断が可能となってきた。3D-SRT(Three-demensional stereotaxic ROI template)は、SPMの標準化機能を利用し、あらかじめ決められた関心領域の局所脳血流を自動的に解析できるが、これらの関心領域についてAlzheimer群、正常群の2群間で比較を行った。

目的：Tl-201心筋血流QGS上の壁運動の定量値について、正常例における標準値を求め、冠動脈造影にて冠動脈病変の確認された虚血性心疾患（IHD）患者と比較した。方法：対象は、Tl-201心筋SPECTを施行したが、心エコー、心電図、臨床経過によって、IHDを否定された10例を正常群（年齢64±8歳）と見なした。IHD例は、冠動脈造影所見によってLAD群4例、LCX群8例、RCA群4例と群分けした。負荷・Tl-201投与直後（早期像）および3時間後（後期像）に、2検出器型ガンマカメラにより、180度収集、R-R間隔8分割により撮像した。結果：正常群の壁運動（mm）は、心尖部、前壁、中隔、後下壁、側壁それぞれ、早期像にて、9.8±1.2、9.3±1.7、6.7±1.6、8.5±1.9、9.8±1.6、後期像にて8.2±1.8、8.4±1.3、4.9±1.9、6.8±1.5、9.7±2.1であった。早期像と後期像の間に、心尖部（p=.0009）、中隔（p=.0018）、後下壁（p=.0025）で壁運動の有意差があった。また、正常群、LAD群、LCX群、RCA群において、早期像、後期像とも、いずれの領

症例は25歳、女性。主訴：右膝・右足関節の腫脹と違和感。膝関節と足関節に単純X-Pで軟部腫瘤と静脈石を認め、MRIでは、T1強調で低信号、T2強調で著明な高信号の腫瘤の内部に線状の低信号を認めた。T2＊強調ではヘモジデリンを示唆する低信号は認めず。画像上、静脈石が存在し、ヘモジデリンの沈着を認めないことから、膝関節と足関節の2関節に発症した滑膜血管腫との診断し、足関節の腫瘤摘出が施行された。滑膜血管腫は1関節に単独で発症するのが一般的であるが、2関節に発症したものは我々が検討した限りでは本例のみであった。同側の多関節に発症したことから、単なる滑膜血管腫というよりは、Klippel-Trenaunay-Weber症候群の不全型の可能性が考えられた。

本研究の目的は、術前化学療法を受ける進行食道癌患者対象に治療開始前FMISO PET/CTで治療効果予測が可能か病理学的評価を踏まえて検討することである。さらにFMISO集積で腫瘍内低酸素やPD-L1やCD8T細胞が発現する腫瘍免疫環境を予測可能か前向き研究で検討する。 科研費交付決定後に近畿大学医学部倫理委員会に研究計画書を提出し、一括申請を行った。倫理委員会で研究実施実施計画が承認された後に食道癌の病理組織標本に免疫染色行うための抗体やFMISOの薬剤合成にかかる消耗品の購入、FMISO PET/CTの検査が円滑に進められるように研究体制を整えた。倫理委員会承認後本研究を開始し、共同研究を行う上部消化管外科と密接に連携して、研究に参加可能な対象者を集め始めた。初年度は研究体制整備が主だった実績となった。 今年度は10症例程度を目標に予定していたが、医学部倫理委員会に申請する研究計画書の作成やその審査にかなり時間を要し、計画に遅れが生じた。次年度からは研究に該当する食道癌患者の収集を第一に努め、収集症例数をあげることである。また、食道癌の術前化学療法後、手術を行った患者の病理染色標本の染色および患者の経過観察に関して円滑に進めていけるように関係各所（近畿大学上部消化管外科、近畿大学病理学講座、久留米大学病院病理部病理診断科、大阪大学大学院医学系研究科情報統合医学講座医学統計学）との連携を再確認して、随時研究の打ち合わせの実施を行う。

本研究は各国の医療に用いられる放射線の使用基準に消化器領域の透視下医療処置の記載がほとんどされていないのは、信頼度の高い実際の被ばく量データが存在しないためであり、各透視下処置における、装置から出力される放射線量、患者・医療従事者の被ばく量を明らかにすることは、現在世に存在しない信頼度の高い情報を得られるのみではなく、「消化器領域のさまざまな透視下処置における被ばく量の基準値を定めDRL設定に繋げる」こと、消化器領域のみならず、透視下医療処置全般に関する被ばく量の基準作りにまで繋がることが可能になると考え立案した。唯一の被ばく国として放射線被ばくに関心の高い本邦において、世界に先駆けて、特に消化器領域の透視下医療処置に関する放射線被ばく量の基準を作成し、世界に発信することを目的に立案した。 「実臨床での透視下手技における患者と医療従事者の被ばく線量集計・解析」については当院における患者への透視下内視鏡手技における被ばく線量測定を行い、その数値は十分に防護対策をとらなければ基準値を容易に超える値であることが判明した。この内容は消化器病学会誌の速報に取り上げられ報告し、日本中の消化器内科医の被ばく防護意識改善に寄与したことが予想される。

ラジウム-223は治療用のアルファ線放出核種として初めて薬事承認された。ただラジウム-223を使った新しい標識化合物の作成は困難である。アルファ線放出核種アスタチン-211は、ヨウ素と性質が類似しており臨床応用が期待されているが、わが国における供給、製造体制は整備されていない。そこでサイクロトロン照射後のターゲットからアスタチン-211を効率的に回収する方法について検討した。アスタチン-211の半減期が7.2時間と短いことから、代謝の早い抗体フラグメントFabを作製し、ヨウ素-125標識体による体内動態およびベータ線放出核種であるイットリウム-90を用いて担がんマウスにおける動物実験を行った。

放射線抵抗性の低酸素領域に集積する18F-ミソニダゾール(F-MISO)を用いたPET/CTによる前向き臨床研究を実施した。合計22例の検査を行ったが、18例では治療前F-MISO-PETでSUV 1.6以上の低酸素領域を認めた。治療前F-MISO SUVmaxが2.0以上のF-MISO高値群は低値群に比較して局所制御率(p=0.03)および全生存率(p=0.004)が有意に不良であった。以上より、多くのヒト腫瘍は低酸素領域を有しており、分割照射で再酸素化現象を示す。また、治療前F-MISO SUVmaxが2.0以上の高値を示す腫瘍は放射線抵抗性であることが示唆された。

PMS-89 Study Group責任研究者 UMIN000004028

放射線抵抗性の低酸素領域に集積する18F-ミソニダゾール(F-MISO)を用いた臨床研究を実 施した。根治照射あるいは術前照射を行った10 例を対象とした。正常筋肉におけるF-MISO SUVmax は、1.26 ± 0.17 であった。これをもとに1.60 SUV(平均 + 2SD)以上のF-MISO 腫瘍内集積を有意な低酸素領域とした。その結果、10 例中9 例では初回検査の腫瘍内F-MISO SUVmax が1.60 SUV 以上で低酸素領域を認めた。また分割照射中に2 回目の撮影の行えた8 例すべてで、再酸素化現象が確認された。

イットリウム-90 標識抗CD20 抗体イブリツモマブチウキセタンによって治療を受けたCD20陽性B 細胞性非ホジキンリンパ腫症例において、治療前後にFDG による糖代謝やFMISO による低酸素のPET/CT イメージングを実施し、その変化を経時的に評価した。またIn-111 標識抗CD20抗体のSPECT/CT を用いたイメージングによって抗原発現も評価した。これら糖代謝、低酸素状態、CD20 の発現と、Y-90 標識抗体による治療効果との関連について解析した。

主任研究者

近年、分子標的の概念や技術が確立され、さまざまの疾患において分子標的を用いた手法が応用されつつあり、ある病態では既に優れた有効性が確認され、診療に不可欠なものとなっている。この分子標的の一分野として、悪性腫瘍を認識するモノクローナル抗体を放射性同位元素で標識し生体に投与して悪性腫瘍の診断や治療を行う抗体シンチグラフィや放射免疫療法は、すでに多くの基礎的検討、臨床応用が進められてきた。本研究は、分子標的の手法を用いて、腫瘍のイメージングおよび治療を目的とした。放射能標識抗HER2抗体を用いた放射免疫療法の実用化に向けて、モノクローナル抗体による内部放射線療法を行うために放射性同位元素と抗体との標識法の諸課題を検討した。マクロサイクルの構造を持つキレート剤は、その標識化合物の安定性によって、放射免疫療法を行う際キレート剤に適していると考えられる。キレートを用いた放射能標識におけるパラメータの設定を行い、動物を用いたヒトの腫瘍モデルで腫瘍標的の条件最適化を検討した。また本研究においては、放射免疫治療に関する基礎的検討として、マウスのモデルにおいて放射能標識した腫瘍細胞の体内分布を調べた。これは、腫瘍をトレーサで標識し細胞の門脈内投与や脾内投与によって肝転移のモデルを確立したものである。肝転移マウスに放射能標識抗体を投与し、その全身の分布や転移巣におけるミクロな分布を確かめた。この肝転移モデルを用いて転移病変を示すトレーサの集積を調べて、放射免疫治療における基礎的解析とした。さらに実際に放射免疫療法の臨床応用を行う場合、放射線防護を考慮し放射線安全基準を順守した診療体制を準備しておくことが不可欠であり、これについても本研究でその要件を考察した。分子イメージングや分子標的治療が次々に臨床応用されている現在、本研究のような基礎的検討の意義は大きいと思われる。

肺小細胞癌はとりわけ従来の治療に抵抗性が高いことから新しい治療法の確立が求められている。肺小細胞癌はNCAM発現率が高いことから、放射免疫治療の対象になると考えられる。今回の検討で、体内分布の結果では、"affinity enhancement system"と名付けられた2ステップ法による放射免疫ターゲッティングを用いることにより1ステップ法に比べて高い腫瘍/正常組織比が実現できた。体内分布のデータを基にした線量計算によると、線量の腫瘍/正常組織比は腫瘍/肝、腫瘍/骨髄比が1ステップ法にて4.2、2.6であるのに対して、2ステップ法にては、14.3、16.8と高い値を得ることができた。これにより、正常組織の線量を抑えながら腫瘍に高い線量を与えることができ、内放射線治療が可能であることが実証された。NCAMは正常の神経組織やNK細胞にも密度は低いが発現されており、放射免疫療法の場合これらの放射線障害が問題になりえる。本2ステップ法においては、2つのBispecific抗体と1つのbivalent haptenとが複合体を形成することによって抗原密度の高い腫瘍の放射能集積は高くなり、正常の神経組織やNK細胞のように抗原密度の低い組織においては複合体ができないため、放射能集積は低くなると考えられる。今回のデータで、肝、腎、肺などにおいて集積および吸収線量が低く抑えられたのは、NCAMの発現密度というよりも、洗い出しが速くなって非特異的集積を抑制できたという面が大きいかもしれない。いずれにしても、2ステップ法によって1ステップ法に比べて高い腫瘍/正常組織コントラストを得られることが明らかとなった。本研究においてNCAM発現腫瘍においてもこれまで報告のあったCEA発現腫瘍と同様に内部放射線治療が可能な高い腫瘍/正常組織比を達成できることが示された。

平成10年度から13年度の4年間にわたる本研究では、高齢者精神障害の内でも、とくにAlzheimer病などによる痴呆診断に対する脳血流SPECTの診断的意義を明らかにすることを目的に多施設読影実験を行った。先ず4施設より診断の確定したAlzheimer病など99症例の脳血流SPECTとMRIを収集し、57症例について核医学を主に専攻する医師10人によって先ず読影実験を行い、その結果をROC解析によって検討した。その結果、1)脳血流SPECTの痴呆鑑別能を表すROC曲線下面積は、すべての医師においてMRIより大であった。しかし統計的に有意の差が有ったのは3人のみであった。対応のあるt-検定でAzの平均値を比較すると、医師全体では、有意にSPEQTの痴呆鑑別能が大であった。2)同じ症例のMRIを放射線科診断医7人が半年後に読影した結果では、医師間の変動は第1の読影実験に比し有意に小さかった。3)SPECT診断の経験が豊富な7人Az平均は、MRI専門医のそれより有意に大であった。すなわち脳血流SPECTはAlzheimer病などの診断に優れていると考えられる。4)SPECT経験の浅い医師の読影結果は、明らかに経験の豊富な医師よりAzが小さかった。これは今後、医師の読影教育が重要である事を示唆するものと考えられる。今後の診断能向上のためには、医師の教育が必要であり、さらには、最近注目...

モノクローナル抗体を放射性同位元素(RI)で標識して悪性腫瘍のイメージングや内部放射線療法を行う試みが現在まで数多くなされているが、RI標識抗体が血中プールや正常組織に留まり病変と正常組織のRI集積比(腫瘍/正常組織比)が不十分である点が問題であった。解決策のひとつとしてpretargetingの方法が考案された。本研究において検討したのは腫瘍関連抗原とハプテンに特異性のあるBispecific Antibody(BsAb)とRI標識ハプテンを用いる方法である(2ステップ法)。癌胎児性抗原CEAを発現している腫瘍をヌードマウスに皮下移植し継代した。さらに1ステップ法として抗CEA抗体を直接I-125標識した。2ステップ法、1ステップ法それぞれのマウスを経時的に屠殺し放射能の体内分布を調べた。マウスにおける体内分布は2ステップ法では、1ステップ法と同等の腫瘍集積が認められた。2ステップ法の腫瘍/正常組織比は早期から高く、腫瘍血液比は5時間後に6、24時間後に37、48時間後に66、96時間後182と極めて高い値に達した。I-125のデータを基にしてI-131を用いた場合の吸収線量を求めると、腫瘍、肝、腎の吸収線量は2ステップ法で5.50、0.15、0.31、1ステップ法で6.80、0.39、0.69cGy/μCiと計算された。2ステップ法を用いて正常組織の被曝を抑えながら腫瘍に治療量の内部放射線照射を行えることを示しており、放射免疫療法への応用が期待される。

我々は従来より、各種シンチグラム検査の臨床的有効性を測定するため、複数の施設が協力して、確定診断付きの画像データベースを作成し、次にこれを多数の医師が読影する実験を行い、ROC解析などを用いて統計解析し、所見検出能や質的診断能およびそれらの医師間変動を定量的、客観的に評価する研究を行ってきた。これらの結果は、文部省科学研究費一般c研究成果報告書「SPECTによる脳疾患診断の精度評価に関する研究(課題番号06670933)にまとめて報告してある。今回の研究では、脳腫瘍の質的診断、特に悪性脳腫瘍の診断に有用と云われ、注目されているT1-201-SPECT像の有効性について、54例の確定診断の得られた症例を対象にして検討を加え、9人の医師による、その読影の結果の変動を評価した。この場合、MRIを参照しない場合とする場合で検討すると、悪性の検出率は、前者で84%、後者で94%であった。良性と悪性の鑑別能を表す医師全体のROC曲線の第1動作点は、MRIを参照しない時TPR:53%、FPR:28%であり、MRI参照時TPR:74%、FPR45%で後者が優れていた。なお、欠損を有するファントムにおけるプロフィルから求めた濃度値と標準偏差、信号対雑音比については、その意義について現在検討を加えている段階である。

モノクローナル抗体を放射性同位元素(RI)で標識して悪性腫瘍のイメージングを行う試みが現在まで数多くなされているが、この際問題となるのがRI標識抗体が血中プールや正常組織に留まり病変と正常組織のRI集積比(腫瘍/正常組織比)が不十分である点であった。解決策のひとつとしてpretargetingの方法が考案された。このうち今回検討したのは癌胎児性抗原CEAとDTPAハプテンに特異性のあるBispecific Antibody(BsAb)とDTPAハプテンを用いる方法である。当初は大腸癌細胞株を用いることを計画しており、それについても実験を行ったが、ヒト甲状腺髄様癌細胞株TTがCEAを発現しているため、これを用いて実験系を作るためにヌードマウスに皮下移植し継代した。2ステップ法のBsAbとして抗CEA/抗DTPA抗体F-6-743を用いた。さらに1ステップ法として抗CEA抗体F6のF(ab')2を用いた。BsAbをヌードマウスの尾静脈から投与した。48時間後、I-125標識DTPAハプテンを投与し、経時的に屠殺し放射能の体内分布を調べた。またI-125標識F6 F(ab')2も体内分布を調べた。マウスにおける体内分布で2ステップ法では、I-125標識F6 F(ab')2を用いる方法と同等の腫瘍集積が見られた。腫瘍/正常組織比は早期から高く、腫瘍血液比は5時間後に6、24時間後に37、48時間後に66、96時間後182と極めて高い値に達した。今回の検討で2ステップ法にて高い腫瘍/正常組織比を得ることができた。観察された高い腫瘍/正常組織コントラストは、甲状腺髄様癌の診断に2ステップ抗体シンチグラフィが有効であることを強く示唆している。また正常組織の被曝を抑えながら腫瘍に治療量の内部放射線照射を行えることも示しており、放射性免疫治療が期待される。