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In this study, it was aimed to investigate  149 Tb-PSMA-617 for targeted α-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer.  149 Tb-PSMA-617 was prepared with >98% radiochemical purity (6 MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors.  149 Tb-PSMA-617 was applied at 1 × 6 MBq (Day 0) or 2 × 3 MBq (Day 0 & Day 1 or Day 0 & Day 3) and the mice were monitored over time until they had reached a pre-defined endpoint which required euthanasia. The tumor growth was significantly delayed in mice of the treated groups as compared to untreated controls (p < 0.05). TAT was most effective in mice injected with 2 × 3 MBq (Day 0 & 1) resulting in a median lifetime of 36 days, whereas in untreated mice, the median lifetime was only 20 days. Due to the β + -emission of  149 Tb, tumor localization was feasible using PET/CT after injection of  149 Tb-PSMA-617 (5 MBq). The PET images confirmed the selective accumulation of  149 Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of  149 Tb for TAT make this radionuclide of particular interest for future clinical translation, thereby, potentially enabling PET-based imaging to monitor the radioligand’s tissue distribution.

Alpha-PET for Prostate Cancer: Preclinical investigation using 149Tb-PSMA-617