Therapeutic efficacy of the radiopharmaceutical [177Lu]Lu-PSMA I&T. Preclinical study

The appearance of radiopharmaceuticals based on prostate-specific membrane antigen (PSMA) ligands labeled with beta- or alpha-emitting radionuclides led to a breakthrough on the development of targeted therapy for metastatic castration-resistant prostate cancer. For the completeness of the preclinical evaluation of therapeutic radiopharmaceuticals based on PSMA, the study of their effectiveness should be supplemented by an assessment of absorbed doses of internal radiation in experimental tumor foci. The objectives of this study were: 1) Examine the dose-effect relationship to assess the therapeutic efficacy of [177Lu]Lu-PSMA I&T with activities comparable to those of humans; 2) Assessing the expected absorbed dose levels created in 22RV1 xenografts after the therapeutic effects have been introduced, with the potential for both minimal and maximum radiopharmaceutical accumulation. The studies were conducted on male nu/nu mice with subcutaneous 22RV1 xenografts. The dynamic of accumulation was examined after 2.2 MBq of a radiopharmaceutical was introduced. The main findings were obtained when [177Lu]Lu-PSMA was introduced at 9.2 MBq (EDmin) and 36.6 MBq (EDmax). A statistically significant dose-dependent inhibition of xenograft growth was found compared with the control. The expected absorbed doses for EDmin in xenografts were between 2.7 Gy for minimal accumulation and 3.9 Gy for maximum accumulation. For EDmax in a similar scenario, this range was 10.7 to 15.5 Gy. The results support the preclinical assessment's informationality in determining the range of doses absorbed in tumor foci that cause the observed therapeutic effects.