Quantitative tumor perfusion imaging with ⁸²Rubidium-PET/CT in prostate cancer – analytical and clinical validation

Abstract

The aim of this work was to evaluate ⁸²Rubidium (⁸²Rb) positron emission tomography (PET) / computed tomography (CT) as a diagnostic tool for quantitative tumor blood flow (TBF) imaging in prostate cancer (PCa). Study 1 was performed to evaluate ⁸²Rb as a marker of TBF, using ¹⁵O-H2O-PET as reference method. Study 2 investigated the ability of ⁸²Rb uptake measurements to differentiate between PCa and normal prostate. Methods: Study 1. Nine PCa patients scheduled for radical prostatectomy were included. Prostate multiparametric magnetic resonance imaging (mpMRI) and both cardiac and pelvic ¹⁵O-H2O-PET and ⁸²Rb-PET were performed. PET findings were compared to post-prostatectomy Gleason grade group (GGG). Study 2. Fifteen primary high-risk PCa patients and 12 controls without known prostate disease were included in a clinical drug trial (EudraCT 2016-003185-26). ⁶⁸Ga-prostate specific membrane antigen (PSMA)-PET/CT scans of PCa patients were available. Pelvic ⁸²Rb-PET was performed. Results: Study 1. Both ⁸²Rb K1 and ⁸²Rb standard uptake values (SUV) correlated strongly with ¹⁵O-H2O TBF (rho=0.95, P < 0.001 and rho=0.77, P = 0.015, respectively). ⁸²Rb-SUV and K1 were linearly correlated (r=0.92, P = 0.001). ⁸²Rb-SUV correlated with post-prostatectomy GGG (rho=0.70, P = 0.03). Study 2. ⁸²Rb-SUV in PCa (3.19 ± 0.48) was significantly higher than prostate ⁸²Rb-SUV in healthy controls (1.68 ± 0.37) (P < 0.001), with no overlap between groups. Conclusion: Study 1 shows that ⁸²Rb-PET/CT can be used for TBF quantification, and that TBF can be estimated by simple SUV; and suggests that ⁸²Rb-SUV is associated with post-prostatectomy GGG and, hence, cancer aggressiveness. Study 2 shows that ⁸²Rb-uptake is significantly higher in PCa than in normal prostate tissue with no overlap between cohorts, confirming the primary hypothesis of the clinical trial. Consequently, ⁸²Rb-PET/CT may have potential as a non-invasive tool for evaluation of tumor aggressiveness and monitoring in non-metastatic PCa.