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 [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). Results: 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. Conclusions: FTT-PET/CT may serve as an alternate biomarker for PARP1 expression and a potential method for PARPi treatment selection.

Original languageEnglish
JournalMolecular Imaging and Biology
DOIs
StateAccepted/In press - 2022

Keywords

  • Cancer
  • FTT
  • PARP
  • PARP inhibitor (PARPi) therapy
  • PET
  • Positron emission tomography

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