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

ABSTRACT: In this study, it was aimed to investigate 149Tb-PSMA-617 for targeted ?-therapy (TAT) using a mouse model of prostate-specific membrane antigen (PSMA)-expressing prostate cancer. 149Tb-PSMA-617 was prepared with >98% radiochemical purity (6?MBq/nmol) for the treatment of mice with PSMA-positive PC-3 PIP tumors. 149Tb-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 ?+-emission of 149Tb, tumor localization was feasible using PET/CT after injection of 149Tb-PSMA-617 (5?MBq). The PET images confirmed the selective accumulation of 149Tb-PSMA-617 in PC-3 PIP tumor xenografts. The unique characteristics of 149Tb 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.

SUBMITTER: Umbricht CA 

PROVIDER: S-EPMC6882876 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature