Abstract
PURPOSE: Localized prostate cancer (PCa) in patients is characterized by a dominant focus in the gland (dominant intraprostatic lesion, DIL). Accurate DIL identification may enable more accurate diagnosis and therapy through more precise targeting of biopsy, radiotherapy and focal ablative therapies. The goal of this study is to validate the performance of [(18)F]DCFPyL PET and CT perfusion (CTP) for detecting and localizing DIL against digital histopathological images. METHODS: Multi-modality image sets: in vivo T2-weighted (T2w)-MRI, 22-min dynamic [(18)F]DCFPyL PET/CT, CTP, and 2-h post-injection PET/MR were acquired in patients prior to radical prostatectomy. The explanted gland with implanted fiducial markers was imaged with T2w-MRI. All images were co-registered to the pathologist-annotated digital images of whole-mount mid-gland histology sections using fiducial markers and anatomical landmarks. Regions of interest encompassing DIL and non-DIL tissue were drawn on the digital histopathological images and superimposed on PET and CTP parametric maps. Logistic regression with backward elimination of parameters was used to select the most sensitive parameter set to distinguish DIL from non-DIL voxels. Leave-one-patient-out cross-validation was performed to determine diagnostic performance. RESULTS: [(18)F]DCFPyL PET and CTP parametric maps of 15 patients were analyzed. SUV(Late) and a model combining K(i) and k(4) of [(18)F]DCFPyL achieved the most accurate performance distinguishing DIL from non-DIL voxels. Both detection models achieved an AUC of 0.90 and an error rate of < 10%. Compared to digital histopathology, the detected DILs had a mean dice similarity coefficient of 0.8 for the K(i) and k(4) model and 0.7 for SUV(Late). CONCLUSIONS: We have validated using co-registered digital histopathological images that parameters from kinetic analysis of 22-min dynamic [(18)F]DCFPyL PET can accurately localize DILs in PCa for targeting of biopsy, radiotherapy, and focal ablative therapies. Short-duration dynamic [(18)F]DCFPyL PET was not inferior to SUV(Late) in this diagnostic task. CLINICAL TRIAL REGISTRATION NUMBER: NCT04009174 (ClinicalTrials.gov).