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A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients - Beyond the Abstract

When is the optimal imaging time for 18F-DCFPyL? The package insert recommends imaging 60 minutes after radiotracer injection and furthermore, discourages imaging beyond 90 minutes, but validated evidence for this is lacking. What has been published is that imaging obtained 120 minutes after 18F-DCFPyL injection depicts more metastatic lesions than imaging at 60 minutes.1,2  Additionally, lesions at 120 minutes have better conspicuity and in one study, 9% of men were upstaged resulting in management changes due to findings on delayed images.3 Our dynamic data suggests later imaging results in higher tumor uptake.

The pharmacokinetic analysis we presented in our paper shows that the reversibility of 18F-DCFPyL binding is negligible in the time span of the two-hour imaging time we measured. We used a two-tissue compartment model to measure the main pharmacokinetic uptake rate, Ki, of the 18F-DCFPyL ligand as it binds to PSMA receptors on the prostate tumor cells. As part of this modeling, we performed experiments in which we left the reversible binding flow rate parameter, k4, float or fixed it at 0. When we let it float, the value measured through the fitting process of the model resulted in a value consistent with zero reversible binding flow rate within measurement error. If we fixed the reversible binding flow rate parameter to zero, the resulting fitted parameters returned lower standard errors. This reflects the continual increase in uptake of 18F-DCFPyL after injection. Extrapolation, therefore, supports scanning at 120 minutes for optimal tumor uptake.

Admittedly, these are small studies and the significance of detecting extra lesions in the metastatic setting is not always clear. Lesions detected only at 2 hours are relatively unusual. Management will likely not change if there are a few additional lesions in someone with many lesions. However, detecting positive lymph nodes beyond the pelvis could dramatically impact treatment decisions. In men with biochemical recurrence, identifying oligometastases early may have value in possibly controlling further spread through aggressive radiation therapy.

There is still much uncertainty regarding the impact of such increased sensitivity on patient outcomes such as survival. From a practical perspective, imaging at 60 minutes or less after 18F-DCFPyL injection, saves time for the patient and enhances workflow. But even with the established 18F-FDG radiotracer, delayed imaging at 2 hours provides better tumor conspicuity than imaging at 1 hour.4 A large retrospective study screening for cancer in the general population in over 3,000 individuals found delayed imaging was more sensitive for tumor detection than standard timepoint scans.5 Specificity and accuracy slightly decreased as more false-positives emerged at the later scan times while positive and negative predictive values were similar at both imaging timepoints. Especially with head and neck cancers, distinguishing tumor from benign tissues can be challenging, and delayed 18F-FDG imaging has proven helpful in this setting.6

One-hour post injection 18F DCFPyl scans are more efficient but there are times when the increased sensitivity of two-hour post injection scanning might be warranted. For instance, in men with high risk prostate cancer planning to undergo initial curative resection, a 2-hour scan might provide more confidence in the stage. In the biochemically recurrent group, with short PSA doubling times or at high risk for other reasons a 2-hour scan is likely to detect lesions not seen at 1-hour post injection.

18F-DCFPyL PET/CT is a sensitive and expensive test. There is little question that 2-hour delayed scans are more sensitive than 1-hour scans. However, a risk adjusted decision to use 2-hours should be considered. In that way, the full potential of 18F DCFPyl scanning can be realized.

Funding: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade name, commercial products, or organizations imply endorsement by the U.S. Government.

Written by: Liza Lindenberg, MD,1 Esther Mena, MD,1 Stephen Adler, MD,2* Peter Choyke, MD1

  1. Molecular Imaging Branch, National Cancer Institute, NIH, Bethesda, MD.
  2. Clinical Research Directorate, Frederick National Laboratory for Cancer Research.

References:  

  1. Rowe SP, Macura KJ, Mena E, et al. PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer. Mol Imaging Biol. 2016;18:411-419.
  2. Szabo Z, Mena E, Rowe SP, et al. Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer. Mol Imaging Biol. 2015;17:565-574.
  3. Wondergem M, van der Zant FM, Knol RJJ, Lazarenko SV, Pruim J, de Jong IJ. 18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution. J Nucl Med. 2017;58:1797-1804.
  4. Kubota K, Itoh M, Ozaki K, et al. Advantage of delayed whole-body FDG-PET imaging for tumour detection. Eur J Nucl Med. 2001;28:696-703.
  5. Naganawa S, Yoshikawa T, Yasaka K, Maeda E, Hayashi N, Abe O. Role of delayed-time-point imaging during abdominal and pelvic cancer screening using FDG-PET/CT in the general population. Medicine. 2017;96:e8832.
  6. Pietrzak AK, Marszalek A, Kazmierska J, et al. Sequential delayed [18 F]FDG PET/CT examinations in the pharynx. Sci Rep. 2020;10:2910.

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