Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition).

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.

Manual on the proper use of meta-[211At] astato-benzylguanidine ([211At] MABG) injections in clinical trials for targeted alpha therapy (1st edition).

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.

Manual on the proper use of sodium astatide ([211At]NaAt) injections in clinical trials for targeted alpha therapy (1st edition).

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.

Calculation of out-of-field dose distribution in carbon-ion radiotherapy by Monte Carlo simulation.

PURPOSE: Recent radiotherapy technologies including carbon-ion radiotherapy can improve the dose concentration in the target volume, thereby not only reducing side effects in organs at risk but also the secondary cancer risk within or near the irradiation field. However, secondary cancer risk in the low-dose region is considered to be non-negligible, especially for younger patients. To achieve a dose estimation of the whole body of each patient receiving carbon-ion radiotherapy, which is essential for risk assessment and epidemiological studies, Monte Carlo simulation plays an important role because the treatment planning system can provide dose distribution only in∕near the irradiation field and the measured data are limited. However, validation of Monte Carlo simulations is necessary. The primary purpose of this study was to establish a calculation method using the Monte Carlo code to estimate the dose and quality factor in the body and to validate the proposed method by comparison with experimental data. Furthermore, we show the distributions of dose equivalent in a phantom and identify the partial contribution of each radiation type. METHODS: We proposed a calculation method based on a Monte Carlo simulation using the PHITS code to estimate absorbed dose, dose equivalent, and dose-averaged quality factor by using the Q(L)-L relationship based on the ICRP 60 recommendation. The values obtained by this method in modeling the passive beam line at the Heavy-Ion Medical Accelerator in Chiba were compared with our previously measured data. RESULTS: It was shown that our calculation model can estimate the measured value within a factor of 2, which included not only the uncertainty of this calculation method but also those regarding the assumptions of the geometrical modeling and the PHITS code. Also, we showed the differences in the doses and the partial contributions of each radiation type between passive and active carbon-ion beams using this calculation method. These results indicated that it is essentially important to include the dose by secondary neutrons in the assessment of the secondary cancer risk of patients receiving carbon-ion radiotherapy with active as well as passive beams. CONCLUSIONS: We established a calculation method with a Monte Carlo simulation to estimate the distribution of dose equivalent in the body as a first step toward routine risk assessment and an epidemiological study of carbon-ion radiotherapy at NIRS. This method has the advantage of being verifiable by the measurement.

Measurement of absorbed dose, quality factor, and dose equivalent in water phantom outside of the irradiation field in passive carbon-ion and proton radiotherapies.

PURPOSE: Successful results in carbon-ion and proton radiotherapies can extend patients' lives and thus present a treatment option for younger patients; however, the undesired exposure to normal tissues outside the treatment volume is a concern. Organ-specific information on the absorbed dose and the biological effectiveness in the patient is essential for assessing the risk, but experimental dose assessment has seldom been done. In this study, absorbed doses, quality factors, and dose equivalents in water phantom outside of the irradiation field were determined based on lineal energy distributions measured with a commercial tissue equivalent proportional counter (TEPC) at passive carbon-ion and proton radiotherapy facilities. METHODS: Measurements at eight positions in the water phantom were carried out at the Heavy-Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences for 400 and 290 MeV/u carbon beams and at the National Cancer Center Hospital East for a 235 MeV proton beam. RESULTS: The dose equivalent per treatment absorbed dose at the center of the range-modulated region H/Dt, decreased as the position became farther from the beam axis and farther from the phantom surface. The values of H/Dt ranged from 6.7 to 0.16 mSv/Gy for the 400 MeV/u carbon beam, from 1.3 to 0.055 mSv/Gy for the 290 MeV/u carbon beam, and from 4.7 to 0.24 mSv/GV for the 235 MeV proton beam. The values of the dose-averaged quality factor QD ranged from 2.4 to 4.6 for the 400 MeV/u beam, from 2.8 to 5.3 for the 290 MeV/u beam, and from 5.1 to 8.2 for the proton beam. The authors also observed differences in the distributions of H/Dt and QD between the carbon and proton beams. CONCLUSIONS: The authors experimentally obtained absorbed doses, dose-averaged quality factors, and dose equivalents in water phantom outside of the irradiation field in passive carbon-ion and proton radiotherapies with TEPC. These data are very useful for estimating the risk of secondary cancer after receiving passive radiotherapies and for verifying Monte Carlo calculations.