Positron Emission Tomography/Computed Tomography Imaging with [18F]PARPi for Precision Guidance of Poly ADP-ribose Polymerase Inhibitor Therapy in Homologous Recombination Repair Mutated and Nonmutated Metastatic Castration-resistant Prostate Cancer.
Academic Article
Overview
abstract
BACKGROUND AND OBJECTIVE: Poly ADP-ribose polymerase (PARP) inhibitors have become an important treatment option for metastatic castration-resistant prostate cancer (mCRPC), targeting PARP1-mediated DNA repair. We investigated [18F]PARPi positron emission tomography (PET) uptake as a predictive biomarker of mCRPC. METHODS: We retrospectively analyzed 15 mCRPC patients who underwent [18F]PARPi PET/computed tomography (CT) examinations and were subsequently treated with PARP inhibitors andrs; homologous recombination repair alterations were detected in two patients. Lesions exhibiting uptake above the background were segmented and quantified. Target to background ratios (TBRs) were derived using the abdominal aorta as a blood pool to normalize interpatient biodistribution. Baseline uptake metrics were correlated with the percentage of prostate-specific antigen (PSA) response. KEY FINDINGS AND LIMITATIONS: Most patients presented with osseous metastases (n = 13) on [18F]PARPi PET, followed by nodal (n = 9), visceral (n = 3), and prostatic (n = 1) lesions. During PARP inhibition, of the 15 patients, six achieved a ≥50% PSA decline, eight showed a <50% decline, and one experienced a >100% PSA increase. The median time to PSA nadir was 40 d (interquartile range [IQR] 20-76 d). The percentage of PSA change correlated well with [18F]PARPi PET mean, peak, and maximum TBRs of bone lesions (all r = 0.72-0.79; all p < 0.05), with weaker, nonsignificant correlations for nodal lesions (r = 0.49-0.53; all p > 0.05). Five patients discontinued treatment due to adverse events (AEs) after a median of 28 d (IQR 27-69 d). Patients without AEs (n = 3) exhibited higher bone lesion TBRs than those with AEs (n = 12, p < 0.05). The limitations of this study are its retrospective nature and small sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS: Baseline [18F]PARPi uptake in mCRPC lesions was associated with a PSA response to PARP inhibition. Higher TBRs particularly in bone lesions predicted a greater PSA decline. These findings support [18F]PARPi PET/CT as a promising tool for patient selection and therapy monitoring, warranting prospective trials with histopathological validation and survival endpoints.
