Short-duration dynamic [18F]DCFPyL PET and CT perfusion imaging to localize dominant intraprostatic lesions in prostate cancer: validation against digital histopathology and comparison to [18F]DCFPyL PET/MR at 120 minutes

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 [18F]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 [18F]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: [18F]DCFPyL PET and CTP parametric maps of 15 patients were analyzed. SUVLate and a model combining Ki and k4 of [18F]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 Ki and k4 model and 0.7 for SUVLate.

Conclusions: We have validated using co-registered digital histopathological images that parameters from kinetic analysis of 22-min dynamic [18F]DCFPyL PET can accurately localize DILs in PCa for targeting of biopsy, radiotherapy, and focal ablative therapies. Short-duration dynamic [18F]DCFPyL PET was not inferior to SUVLate in this diagnostic task.

Clinical trial registration number: NCT04009174 (ClinicalTrials.gov).

Keywords: CT perfusion; Dominant intraprostatic lesion (DIL); Prostate-specific membrane antigen (PSMA); Tracer kinetic modelling; [18F]DCFPyL.

Conflict of interest statement

The CT perfusion software is licensed to GE Healthcare (Ting-Yim Lee). All other authors have no competing interests to report.

© 2021. The Author(s).

Figures

Fig. 1

Registration pipeline. CT Computed tomography, T2w transverse relaxation time weighted, PET positron emission tomography, MR magnetic resonance, BF blood flow, BV blood volume, MTT mean transit time, PS vessel permeability surface product, To contrast delay time, K1 influx rate constant, k2 efflux rate constant, k3 binding rate constant, k4 dissociation rate constant, Ki net uptake rate constant, DV distribution volume, SUV standardized uptake value

Fig. 2

Flow diagram showing patient enrolment. *Registration failed because the in vivo prostate was significantly deformed relative to explanted prostate due to gas in the rectum. FCH Fluorocholine, DCFPyL 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid

Fig. 3

Comparison of leave-one-patient-out cross-validation metrics of the different DIL detection models—error rate (ER), false-positive rate (FPR), false-negative rate (FNR), and AUC. Error bars are the standard deviation of mean. A significant difference (P < 0.05) is marked with asterisk (*) for P < 0.05 and double asterisk (**) for P < 0.001. Ki Net uptake rate constant, k4 dissociation rate constant, SUVLate 2-h post-injection standardized uptake value, SUVEarly 10-min post-injection standardized uptake value, BF blood flow, MTT mean transit time, ER error rate, FPR false-positive rate, FNR false-negative rate, AUC area under the curve of receiver operating characteristic curve, DIL dominant intraprostatic lesion

Fig. 4

Example of the co-registered in vivo images and parametric maps. The location of DIL is outlined in black. CT Computed tomography, PET positron emission tomography, SUVLate 2-h post-injection standardized uptake value, Ki net uptake rate constant, k4 dissociation rate constant, SUVEarly 10-min post-injection standardized uptake value, BF blood flow, BV blood volume, DIL dominant intraprostatic lesion