Pilot Study: PARP1 Imaging in Advanced Prostate Cancer
Farrokh Dehdashti, Melissa A. Reimers, Kooresh I. Shoghi, Delphine L. Chen, Jingqin Luo, Buck E. Rogers, Russell K. Pachynski, Sreeja Sreekumar, Cody Weimholt, Dong Zhou
Abstract
Abstract Purpose PARP inhibitor (PARPi) therapy is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) genomic aberrations. However, only a fraction of patients with BRCA1/2 mutations respond to PARPi therapy. In this pilot study, we assess PARP-1 expression in prostate cancer patients with and without HRR genomic alternations using a novel PARP-based imaging agent. Procedures Nine advanced prostate cancer patients were studied with PET/CT and [ 18 F]FluorThanatrace (FTT), an analogue of the PARPi rucaparib. Images were analyzed using maximum standardized uptake values (SUV max ). PARP expression was assessed by immunohistochemistry (IHC) when feasible ( n = 4). Results We found great variability in FTT uptake (SUV max range: 2.3–15.4). Patients with HRR mutations had a significantly higher SUV max ( p = 0.0379) than patients with non-HRR mutations although there was an overlap in FTT uptake between groups. Three patients without HRR and one with HRR mutations had similarly high PARP1 IHC expression. Conclusions FTT-PET/CT may serve as an alternate biomarker for PARP1 expression and a potential method for PARPi treatment selection.