Current treatments for prostate cancer, such as chemotherapy and androgen receptor signaling inhibitors, have varying success rates with unpredictable outcomes. As a result, there is a need for the development of novel targeted therapies which can provide positive responses from patients. Radioligand therapy (RLT) in combination with poly (ADP-ribose) polymerase (PARP) inhibitors has shown efficacy in preliminary in vitro studies. In this study, we will use RLT with beta emitter 177-Lu and alpha emitters 227-Th and 225-Ac conjugated to a CD46 targeting antibody, in addition to Niraparib or Talazoparib as the PARP inhibitor. MTT and colony forming assays were performed on two prostate cancer cell lines. 225-Ac-YS5 in combination with Talazoparib showed a promising ZIP synergy score of 25.35, indicating that the two work synergistically to provide better therapeutic outcomes. After in vitro efficacy, we will test in murine models, with a future goal of a human clinical trial.