[ 18 F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response

The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways—such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [ 18 F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [ 225 Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [ 18 F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [ 18 F]-PARPZ to facilitate clinical translation in the ⍺-therapy space.