Dosimetric support for clinical trials of the alpha-emitting radiopharmaceutical Ac-225-PSMA-617 at radionuclide therapy of metastatic castration-resistant prostate cancer

To calculate internal radiation doses to tumors and organs at risk of patients included to clinical trials of 225Ac-PSMA-617 radiopharmaceutical, a specialized software and database package, developed at the National Medical Research Radiological Center, was used. The calculations were based on the general methodology of Medical Internal Radiation Dose (MIRD) Committee. Visualization of foci and organs at risk of patients was performed using the SPECT/CT method (Discovery NM/CT 670 system) with a high-energy collimator and recording photopeaks of gamma radiation of 221Fr (218 keV) and 213Bi (444 keV) at discrete points in time after the administration of the radiopharmaceutical (1-72 hours). The values of internal equivalent doses were determined for all visualized foci and organs at risk (parotid and submandibular salivary glands, kidneys, spleen, liver). The relative biological efficiency for alpha particles was accepted to be 5. A large variability of individual radiation doses in foci was found at the same administered radiopharmaceutical’s activity: dose values differ by 7-9 times depending on individual foci volumes and individual patients’ pharmacokinetic parameters. At the same time, equivalent doses in foci tend to increase with increasing of administered radiopharmaceutical activity, and are within the following limits: 7-33 Sv (planned activity for administration – 6 MBq) and 6.4-55 Sv (planned activity for administration – 9 MBq). Individual equivalent doses to organs at risk also vary significantly and are within the following limits: 0.1-1.5 Sv (salivary glands) and 0.68-8.8 Sv (kidneys, spleen, liver), which is less than the “commonly applied dose constraints” in radiotherapy. The data obtained are necessary for the analysis of the effectiveness and safety of the 225Ac-PSMA-617 radiopharmaceutical and allow optimizing the choice of radiopharmaceutical’s activity individually for each patient.