A proof-of-concept study of quantitative tumor perfusion imaging with ⁸²Rb PET/CT in Prostate Cancer

Objectives: Tumor blood flow (TBF) is a known marker of cancer aggressiveness and has been used to monitor treatment response in a range of cancers. Recently, access to the flow tracer ⁸²Rb has been improved due to rise in cardiac PET, providing a possibility to quantify TBF in a cost-effective and simple way using ⁸²Rb PET. This study aimed at evaluating the potential usefulness of ⁸²Rb PET as a marker of TBF in prostate cancer (PCa).

Methods: Eight patients with biopsy-verified PCa scheduled for radical prostatectomy were included in a validation study and ⁸²Rb kinetics were quantitatively compared to the gold standard of ¹⁵O-water PET with radial artery blood sampling. All patients underwent multiparametric MRI to delineate the tumor. In a GCP monitored proof-of-concept (PoC) study 15 patients with high-risk PCa, who had undergone ⁶⁸Ga-PSMA PET/CT and random prostate biopsies, were included in the study. An ⁸²Rb PET was performed of the pelvic region and subsequently fused to ⁶⁸Ga-PSMA PET/CT, for delineation of tissues for ROI/VOI analysis. A control group was defined consisting of 12 patients with no known disease of the prostate referred for myocardial blood flow examination. Results: In the validation study both ⁸²Rb K1 and ⁸²Rb SUV correlated strongly with ¹⁵O-water TBF (rho=0.95, p<0.001 and rho=0.86, p=0.003, respectively). ⁸²Rb SUV and K1 were linearly correlated (r=0.91, p=0.002). ⁸²Rb SUV correlated with post-prostatectomy Gleason Grade Group (rho=0.70, p=0.03). In the PoC study ⁸²Rb SUV was significantly higher than ⁸²Rb SUV in control prostates, with no overlap between groups, both when the tumors were drawn by PSMA guidance (p<0.001) and when applying a standardized 60% threshold on the ⁸²Rb prostate hot spot (p<0.001). Conclusions: This study qualifies ⁸²Rb PET for TBF estimation in PCa by 1) validating TBF measurement by ⁸²Rb PET against ¹⁵O-water PET, the gold standard method of perfusion, 2) demonstrating that TBF can be measured from ⁸²Rb PET using static SUV, and 3) demonstrating that ⁸²Rb SUV in PCa is significantly higher than in healthy prostate tissue. Furthermore, the study suggests that the ⁸²Rb SUV is associated with post-prostatectomy Gleason Grade and hence aggressivity of the cancer. ⁸²Rb PET can be used to measure tumor blood flow and might be a valuable non-invasive tool for evaluation of tumor aggressiveness and monitoring in PCa and potentially other malignancies. Financial support: This work was financially supported by The Danish Cancer Society and Health Research Fund of Central Denmark Region.