Work

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

Year: 2022

Type: article

Abstract: ABSTRACT Motivation 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. Materials and Methods 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 analyzed, along with and correlative autoradiography and histology acquired. Results [ 18 F]-PARPZ was able to distinguish treated from control (saline) xenografts by 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. Conclusions Together, these data support expanded investigation of [ 18 F]-PARPZ to facilitate clinical translation in the α -therapy space.

Source: Scientific Reports

DOI: 10.1038/s41598-022-17460-0