18F-FluorThanatrace (18F-FTT) positron emission tomography (PET/CT) in prostate cancer measures in vivo PARP-1 expression and is associated with adverse clinicopathologic features.
Authors: Taunk Neil , Carlin Sean , Lee David , Sadiq Shaan , Bhageri Sina , Schwartz Lauren , Mangone Ciera , Dulal Christina , Makvandi Mehran , Schubert Erin , Mach Robert , Pryma Daniel , Pantel Austin 
Published: June 2022

5030

Background: We performed the first clinical trial to evaluate expression of PARP-1, the target of PARP-inhibitors (PARPi), in prostate cancer (PC) using 18F-FluorThanatrace (18F-FTT), a novel radiopharmaceutical that selectively measures PARP-1 expression with PET/CT. Approvals for PARPi in metastatic castrate resistant prostate cancer (mCRPC) have improved clinical outcomes in men with homologous recombination deficient (HRD) associated PC. Patient selection using genetic biomarkers such as HRD and PARP-1 IHC are insufficient PARPi biomarkers. We report the first trial of assessment of PARP-1 expression in men with prostate cancer. Methods: Men with localized PC with planned prostatectomy were included. Patients were required to have 2+ biopsy cores with > 50% involvement, OR > 1cm dominant prostate lesion on MRI. Men received a single pre-operative [18F]FTT scan. [18F]FTT is. Patients received a single injection of 8-12 mCi [18F]FTT and underwent 60 minutes dynamic scanning and static scan at 90 minutes post-injection. Ex vivo IHC, autoradiography, and germline/somatic genomic testing was performed after surgical removal. The study was approved by the University of Pennsylvania IRB (UPCC #13817, ClinicalTrials.gov, NCT03334500). Results: 30 men consented for participation (29 with presurgical MRI) from 6/2019 to 12/2020. Mean PSA was 9.8 ng/mL (range 2.35 – 60). Gleason Grade (GG) groups included: GG 1 (n = 1), GG 2 (n = 10), GG 3 (n = 5), GG 4 (n = 7), and GG 5 (n = 7). Stages included: pT2 (n = 12), pT3a (n = 10), pT3b (n = 8). Two patients had pN1 disease (cN0 by MRI). Mean injected dose was 10.32 mCi (range 7.52 – 11.62). There were no serious adverse events noted for any patient. Of patients with presurgical MRI, a range of uptake on the PET/CT correlated to the dominant lesion on MRI. The mean and median SUVMax of all lesions was 3.52 and 3.46, respectively (range 1.03 – 6.56). Both patients cN0 on MRI, had those nodes identified on the [18F]FTT scan. SUVMax was significantly associated with increasing Gleason Grade group Rs = 0.37298, p (2-tailed) = 0.04. SUVMax was significantly associated with Decipher scores (GenomeDx Biosciences, San Diego, CA) Rs = 0.63077, p (2-tailed) = 0.02. Ex vivo IHC showed PARP1 localization to the dominant region on the MRI. Ex vivo autoradiography using [I125]KX1, a FTT analogue, and correlation to genomic HRD (DDR aberrations and HRD scores) is underway. Conclusions: [18F]FTT detects in vivo PARP-1 expression in prostate cancer and SUVMax is associated with higher Gleason Grade groups and Decipher scores, This tracer may be used as an imaging biomarker for PARP-1 expression in men with prostate cancer, the target of PARPi. A follow-up study to assess change in [18F]FTT uptake before and after administration of PARPi in men with mCRPC is underway to test [18F]FTT as a biomarker PARPi (UPCC #08821). Clinical trial information: NCT03334500.