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.
Nine advanced prostate cancer patients were studied with PET/CT and [18F]FluorThanatrace (FTT), an analogue of the PARPi rucaparib. Images were analyzed using maximum standardized uptake values (SUVmax). PARP expression was assessed by immunohistochemistry (IHC) when feasible (n = 4).
We found great variability in FTT uptake (SUVmax range: 2.3-15.4). Patients with HRR mutations had a significantly higher SUVmax (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.
FTT-PET/CT may serve as an alternate biomarker for PARP1 expression and a potential method for PARPi treatment selection.
Molecular imaging and biology. 2022 Jun 14 [Epub ahead of print]
Farrokh Dehdashti, Melissa A Reimers, Kooresh I Shoghi, Delphine L Chen, Jingqin Luo, Buck Rogers, Russell K Pachynski, Sreeja Sreekumar, Cody Weimholt, Dong Zhou
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA. ., Department of Internal Medicine, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA., Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA., Department of Radiology, University of Washington, Seattle, USA., Department of Surgery, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA., Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA., Department of Pathology and Immunology, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.