Abstract Background A post-marketing surveillance (PMS) study was conducted in Japan to assess real-world outcomes with radium-223 treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Results from the treatment period showed that radium-223 was generally well tolerated. Follow-up was subsequently extended to 3 years to collect data on fracture events. Results of the extended follow-up are now reported. Methods This prospective, non-interventional, multicenter, single-cohort PMS study enrolled men with CRPC and bone metastases treated with radium-223 under clinical practice. Extended follow-up lasted until 3 years after the first administration of radium-223. Data on clinical fractures and survival were collected. Results A total of 334 patients were enrolled, with a median follow-up of 15.3 months (range 1–50). The overall incidence proportion of fractures reported as adverse events was 7.76% (95% confidence interval [CI] 5.09–11.25%), with a fracture incidence rate of 5.22 patients [with fracture]/100 person-years (PY). Patients who received bone-modifying agents (BMAs) had a numerically lower incidence of fractures (5.85%; 3.46/100PY vs 9.93%; 7.92/100PY). Median overall survival was 26.32 months (95% CI 21.65-not reached). Conclusion Compared with existing reference data, there was no obvious increase in the incidence of clinical fractures in Japanese patients with mCRPC who were treated with radium-223 under clinical practice. As is already well known for androgen deprivation, BMAs may also be useful in reducing bone fracture after radium-223.

Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; data from three parts are presented here. Part 1 evaluated safety and tolerability; Parts 2 (post-taxane) and 3 (pre-taxane/taxane-naive) assessed the overall response rate (ORR; primary endpoint), overall survival (OS), radiographic progression-free survival (rPFS), disease control rate (DCR), PFS, and safety; and Part 4 is the expansion part. Patients received 7.4 GBq (±10%) 177Lu-PSMA-617 Q6W for up to six cycles. Results: Of the 35 patients who underwent a [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT scan, 30 received 177Lu-PSMA-617 (post-taxane, n = 12; pre-taxane, n = 18). No dose-limiting toxicity was noted in Part 1 (n = 3). Post- and pre-taxane patients had a median of three and five cycles, respectively. The primary endpoint, ORR, met the pre-specified threshold, with the lower limit of the 90% confidence interval (CI) above the threshold of 5% for post-taxane and 12% for pre-taxane. Post- and pre-taxane patients had an ORR of 25.0% (90% CI: 7.2–52.7) and 33.3% (90% CI: 15.6–55.4), respectively. In post- and pre-taxane patients, the DCR was 91.7% and 83.3%, the median rPFS was 3.71 and 12.25 months, and the median PFS was 3.71 and 5.59 months, respectively. The median OS was 14.42 and 12.94 months in post- and pre-taxane patients, respectively. The most common adverse events were constipation, decreased appetite, decreased platelet count, anemia, and nausea. Conclusions: The primary endpoint (ORR) was met. The safety profile of 177Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC.

①目的 [⁶⁴Cu]Cu-ATSMを患者に投与した際の病室内における空気中放射能濃度を測定することにより，[⁶⁴Cu]Cu-ATSMを投与した患者を特別措置病室に入院させるための要件を満たすことを確認する．②方法 悪性神経膠腫患者3例に対し，[⁶⁴Cu]Cu-ATSM（100 MBq/kg±10%）の静脈内投与を放射線治療病室内において行い，病室内の各2箇所（部屋の中央と入り口付近）について，ろ過捕集方法により空気中放射能濃度を測定した．③結果 測定された空気中放射能濃度は検出限界（8.24×10⁻⁷ Bq/cm³又はそれ以下）付近又はそれ未満であり，⁶⁴Cuの法定空気中濃度限度1×10⁻¹ Bq/cm³の10,000分の1以下と基準値を大きく下回ることが確認された．④結論 [⁶⁴Cu]Cu-ATSM投与患者を特別措置病室に入院させるために必要な空気中放射能濃度に関する適用条件は満たされることが示された．

BACKGROUND/AIM: This study aimed to clarify the feasibility of creating coplanar single-isocenter volumetric modulated arc therapy (SI-VMAT) with a Halcyon using a knowledge-based planning system based on non-coplanar plans for treating multiple brain metastases. PATIENTS AND METHODS: A knowledge-based RapidPlan (RP) planning model was built using 32 TrueBeam SI-VMAT plans including one full arc and three non-coplanar partial arcs. To confirm its applicability across different beam geometries using the Halcyon system, the model was validated on the basis of the root-mean-square error (RSME), deviation rate, and absolute differences between estimated and actual dose-volume histograms (DVHs). Dosimetric performance of TrueBeam and Halcyon plans was then compared for 10 patients. RESULTS: The average RSME values for the Halcyon and TrueBeam plans were 0.75±0.40 Gy and 0.46±0.28 Gy, respectively (p<0.05). Using the model for Halcyon plan creation, deviations from the estimated DVH boundaries were mainly observed in the low-dose region (<9 Gy), while the actual DVH closely aligned with the estimated DVH in the intermediate- and higher-dose regions. For comparison of dosimetric performance, statistically significant differences were found in the gradient index, conformity index, and normal brain volumes receiving ≥12 Gy, ≥18 Gy, and ≥27 Gy. However, these differences were deemed clinically negligible, with less than 1% disparity in the above doses to the normal brain. CONCLUSION: The RP model can effectively predict doses for Halcyon, regardless of different beam configurations. Coplanar SI-VMAT with Halcyon can feasibly be used in clinical applications, such as the treatment of multiple brain metastases.

Background: Although several reports have compared the outcomes of self-expandable metallic stent (SEMSs) and transanal decompression tube (TDT) placement for malignant colorectal obstruction (MCO), few studies have compared the radiation exposure (RE) associated with these two procedures. Consequently, we aimed to compare the RE of SEMS and TDT placements for MCO using propensity score matching (PSM) in a multi-center, prospective observational study. Methods: This study investigated the clinical data of 236 patients who underwent SEMS or TDT placement. The air kerma at the patient entrance reference point (Ka,r: mGy) and air kerma–area product (PKA; Gycm2) were measured and compared between SEMS and TDT groups after PSM. Results: After PSM, 61 patients were identified in each group. The median Ka,r in the SEMS group was significantly greater than that in the TDT group (77.4 vs. 55.6 mGy; p = 0.025) across the entire cohort. With respect to subgroup analyses by location, in the rectum, the median Ka, r and PKA were significantly greater in the SEMS group than in the TDT group (172.9 vs. 34.6 mGy; p = 0.001; and 46.0 vs. 18.1 Gycm2; p = 0.006, respectively). However, in the colon, the RE parameters did not significantly differ between the two groups. Conclusions: TDT might be a more suitable option for decompression in patients with malignant rectal obstruction due to its lower RE and technical advantages. Conversely, SEMS placement is recommended as the first decompression method to treat malignant colonic obstruction, in line with the current guidelines.

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.

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.

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.

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。

[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.

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。

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 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...

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。

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。

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.

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。

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.

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.

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。

本研究は消化器内科領域における透視下内視鏡手技を使用される放射線被ばく線量により高被ばく手技、中等度被ばく手技、低被ばく手技とグレーディングすることを研究目的の主としている。透視下内視鏡手技は多岐に渡り、各施設で放射線の使用状況も異なるため、単施設での測定は大きなバイアスが発生するため、全国多施設での測定が必要である。本研究責任者の竹中完は全国多施設前向き放射線線量測定を行うために研究グループ（REX-GI group）を発足し、さまざまな透視下内視鏡手技の放射線被ばく線量測定を行い、グループとして国内外の学会発表、英文論文作成を行ってきた。2023年度は本研究に関連する消化器内科領域の透視下手技における被ばく防護に関する英文論文が4本（すべて査読あり、採択ジャーナル：JGH Open,Sci Rep, Br J Radiol, DEN Open）採択された。また米国消化器病週間(DDW2023)、第103回日本消化器内視鏡学会総会において上記内容を学会発表した。 本研究は胆膵疾患（膵癌・胆道癌・急性膵炎・慢性膵炎・膵嚢胞性疾患・胆石等）に対する透視下内視鏡手技における使用放射線被ばく線量測定を全国多施設で行うことが必須であるが、上述のREX-GIにて測定は終えており、一万を超えるデータを取得している。現在解析を行っているが、その中で実際に手技を行う医療従事者の放射線被ばくの現状も明らかにする必要性が浮上し、測定を検討している。測定に際しては各施設で放射線の使用方法、放射線被ばく対策方法が異なるため、研究責任者が各施設を訪問し、現状確認する必要があるがコロナ感染症による施設規制によって訪問規制がかかっていた。2024年度は各施設規制が緩和しているため早々に測定を開始できる見込みである。

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。