PURPOSE: [18F] Poly-ADP-ribose polymerase inhibitors (PARPi), a novel radiotracer, enables visualization of PARP1 upregulation by PET imaging. Here, we aimed to quantify PARPi uptake in tumor lesions of metastatic castration-resistant PCa (mCRPC) patients and perform a comparison with prostate specific membrane antigen (PSMA) expression using PET/CT scans. METHODS: Data from 22 male patients with mCRPC, who underwent [18F]PARPi and [68Ga]Ga-PSMA-11 PET/CT scans, were retrospectively quantified. Lesions with relevant PARPi uptake (higher than background) were delineated and correlated with their [68Ga]PSMA uptake using standardized uptake values (SUV). Additionally, a comparison was performed to investigate the effects of homologous recombination deficiency (HRD) alterations on PARPi tumor uptake. RESULTS: The majority of metastatic PCa lesions that exhibited PARPi uptake were located in the bones (n = 57), with mean SUVmax values of 4.9 ± 1.5 for PARPi and 30.9 ± 28.3 for [68Ga]PSMA. Additionally, 3 local prostate lesions, 14 lymph nodes and 4 further metastatic lesions were detected. Significant correlations were identified between PARPi- and [68Ga]PSMA uptake, as measured by SUVmean (r = 0.48, p < 0.001), SUVpeak (r = 0.48, p < 0.001) and SUVmax (r = 0.43, p < 0.001) of the osseous metastatic lesions and SUVpeak (r = 0.49, p = 0.04) of extraosseous lesions. No significant differences were found between PARPi uptake of metastatic lesions in patients with or without HRD alterations (all p > 0.05). CONCLUSION: Results showed a considerable uptake of [18F]PARPi in mCRPC patients and indicated a correlation between PARPi uptake and PSMA expression, suggesting the potential of using [18F]PARPi as a diagnostic imaging tool in mCRPC patients. More studies are needed to evaluate the clinical benefit of this innovative radiotracer.

Department of Biomedical Imaging and Image Guided Therapy Division of General and Pediatric Radiology Medical University of Vienna Vienna 1090 Austria

Department of Biomedical Imaging and Image guided Therapy Division of Nuclear Medicine Medical University of Vienna Währinger Gürtel 18 20 Vienna 1090 Austria

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology University of Texas Southwestern Medical Center Dallas USA

Department of Urology Weill Cornell Medical College New York USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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