Search

Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients' caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of 177Lu‐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 177Lu‐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: 177Lu‐DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 . [ABSTRACT FROM AUTHOR]

We present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha 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 on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well. [ABSTRACT FROM AUTHOR]