Kinetic analysis of dominant intraprostatic lesion of prostate cancer using quantitative dynamic [(18)F]DCFPyL-PET: comparison to [(18)F]fluorocholine-PET

PURPOSE: Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [(18)F]DCFPyL (2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [(18)F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [(18)F]FCH and [(18)F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron emission tomography (PET). METHODS: 19 and 23 PCa patients were evaluated with dynamic [(18)F]DCFPyL and [(18)F]FCH PET, respectively. The dynamic imaging protocol with each tracer had a total imaging time of 22 min and consisted of multiple frames with acquisition times from 10 to 180 s. Tumour and benign tissue regions identified by sextant biopsy were compared using standardized uptake value (SUV) and tracer kinetic parameters from kinetic analysis of time-activity curves. RESULTS: For [(18)F]DCFPyL, logistic regression identified K(i) and k(4) as the optimal model to discriminate tumour from benign tissue (84.2% sensitivity and 94.7% specificity), while only SUV was predictive for [(18)F]FCH (82.6% sensitivity and 87.0% specificity). The higher k(3) (binding) of [(18)F]FCH than [(18)F]DCFPyL explains why [(18)F]FCH SUV can differentiate tumour from benign tissue within minutes of injection. Superior [(18)F]DCFPyL tumour contrast was due to the higher k(4)/k(3) (more rapid washout) in benign tissue compared to tumour tissue. CONCLUSIONS: DIL was detected with good sensitivity and specificity using 22-min dynamic [(18)F]DCFPyL PET and avoids the need for delayed post-injection imaging timepoints. The dissimilar in vivo kinetic behaviour of [(18)F]DCFPyL and [(18)F]FCH could explain their different SUV images. Clinical Trial Registration NCT04009174 (ClinicalTrials.gov).