Evaluation of Radiation Safety of Radiopharmaceutical Based on 177Lu-Dota-PSMA in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Abstract

Purpose: To evaluate the safety and efficacy of radionuclide therapy with the radiopharmaceutical 177Lu-DOTA PSMA in patients with metastatic castration-resistant prostate cancer. Material and methods: A total of 27 male patients with histologically confirmed metastatic prostate cancer and multiple metastatic lesions detected by positron emission tomography with high uptake of 18F-PSMA or 68Ga-PSMA were examined. The patients received radionuclide therapy with a single intravenous administration of the radiopharmaceutical 177Lu-DOTA-PSMA in subgroups with treatment activities ranging (0.637‒5.59), (6.81‒7.58), and (9.07‒10.5) GBq. To assess adverse radiation exposure, a biological dosimetry method based on the analysis of chromosome aberrations in blood lymphocytes was used. Peripheral blood samples were collected from the cubital vein before therapy and again after the administration of 177Lu-DOTA-PSMA. Chromosomal aberrations were analyzed using the standard metaphase method in cells in the first mitosis with cell incubation for 48 hours. The following chromosomal aberrations were analyzed: acentrics (ace: paired fragments and dots), centric rings (rc), and dicentrics (dic). The number of analyzed metaphases per patient ranged from 81 to 650, with an average of 314. A total of 21 563 metaphases in 68 blood samples were analyzed. Adverse radiation effects on the patient’s body were assessed based on the induction (increase) of chromosomal aberrations in blood lymphocytes, using a calibration dose curve previously obtained in our laboratory through in vitro experiments. Statistical processing of the results and regression analysis were performed using standard algorithms provided in Microsoft Excel and OriginLab. Results: An increase in the mean frequency and median distribution for all three aberration combinations (ace+rc+dic), (rc+dic), and dic was found with increasing therapeutic activity of the administered radiopharmaceutical. The average adverse doses in subgroups were: 0.96±0.77 Gy in group I; 2.43±0.43 Gy in group II; and 2.69±0.36 Gy in group III, respectively. The average doses in subgroups II and III did not statistically differ from each other but significantly exceeded the dose in subgroup I (p<0.05). The dose coefficient for adverse radiation exposure to bone marrow in the examined patients was estimated to be within the range of (0.27–0.38) Gy/GBq. The average absorbed doses for individual patients exceeded the established safe limit of 2 Gy in 11.8% of patients in subgroup I, 44.4% in subgroup II, and 70% in subgroup III. Conclusion: When treating patients diagnosed with metastatic castration-resistant prostate cancer with 177Lu-DOTA-PSMA, the absorbed dose in the red bone marrow may exceed the established safe limit of 2 Gy in a significant proportion of patients. The trend toward increased absorbed dose to the red bone marrow following administration of 177Lu-DOTA-PSMA, noted in recent years, is confirmed.