Phase 2 18F-fluorthanatrace (FTT) PARP1-targeted PET tracer to predict PARPi response

Washington University School of Medicine is running a multicenter, open-label diagnostic study testing whether 18F-fluorthanatrace (18F-FTT), a PARP1-directed PET imaging tracer, can help predict response to standard-of-care PARP inhibitor therapy in metastatic prostate cancer, alongside EnhanceAR-Seq circulating tumor DNA profiling. Participants with metastatic castration-resistant prostate cancer, homologous recombination repair mutations, and ongoing androgen-deprivation therapy undergo FTT-PET/CT at baseline and again approximately 2 weeks after starting a PARP inhibitor, with serial ctDNA collected at baseline, after cycle 1, at 12 weeks, and at progression. The scientific angle is combining a noninvasive readout of PARP1 tracer uptake with blood-based genomics to test whether imaging and molecular changes can identify HRR-mutated tumors that are unlikely to benefit from PARP inhibition or are developing resistance. Current treatment for HRR-mutated mCRPC can include PARP inhibitors, androgen-receptor pathway therapy, taxanes, and radioligand therapy depending on mutation, prior treatment, and disease setting; this study aims to add an early treatment-response tool rather than introduce a new therapy.