Reviews and CommentaryFree Access

18F-DCFPyL PET/CT in Men with Prostate Cancer

Published Online:https://doi.org/10.1148/radiol.221536

See also the article by Ulaner et al in this issue.

Katherine Zukotynski, MD, PhD, is a professor at McMaster University. She                     holds certifications from the American Board of Radiology, the American Board of                     Nuclear Medicine, and the Board of Nuclear Cardiology. She is a fellow of the                     Royal College of Physicians and Surgeons of Canada, the Society of Nuclear                     Medicine and Molecular Imaging, and the American College of Nuclear                     Medicine.

Katherine Zukotynski, MD, PhD, is a professor at McMaster University. She holds certifications from the American Board of Radiology, the American Board of Nuclear Medicine, and the Board of Nuclear Cardiology. She is a fellow of the Royal College of Physicians and Surgeons of Canada, the Society of Nuclear Medicine and Molecular Imaging, and the American College of Nuclear Medicine.

Phillip Kuo, MD, PhD, trained in internal medicine, nuclear medicine, and                     radiology and is professor of medical imaging, medicine, and biomedical                     engineering at University of Arizona, where he previously served as chief of                     nuclear medicine for 10 years. He is also senior medical director for Invicro,                     an imaging CRO. He has more than 100 peer-reviewed publications and has served                     as PI or co-PI on numerous NIH grants and clinical trials.

Phillip Kuo, MD, PhD, trained in internal medicine, nuclear medicine, and radiology and is professor of medical imaging, medicine, and biomedical engineering at University of Arizona, where he previously served as chief of nuclear medicine for 10 years. He is also senior medical director for Invicro, an imaging CRO. He has more than 100 peer-reviewed publications and has served as PI or co-PI on numerous NIH grants and clinical trials.

In the past, the main tools for imaging the prostate gland were US and MRI. CT and technetium 99m (99mTc) methylene diphosphonate (MDP) bone scanning were used to assess disease spread. Recently, PET using radiopharmaceuticals that target the prostate-specific membrane antigen (PSMA), called PSMA PET, is being increasingly performed to detect sites of prostate cancer at initial staging and biochemical recurrence. Several PSMA PET radiopharmaceuticals are available. The most commonly encountered radiopharmaceuticals are gallium 68 (68Ga) PSMA-11, fluorine 18 (18F) 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (DCFPyL), and 18F–PSMA-1007.

Overall, the literature suggests these PSMA radiopharmaceuticals for PET have similar sensitivity and specificity in the detection of prostate cancer (1,2). Sites of prostate cancer are readily detected with PSMA PET when the disease is occult at CT and 99mTc-MDP bone scanning. This is particularly the case for PSMA PET when the prostate-specific antigen (PSA) level is high and/or the PSA doubling time is high. A systematic review and meta-analysis by Perera et al (3) from 2020 of 37 articles, including 4790 men, reported the number of positive PSMA PET scans was 33% with a PSA level less than 0.2 ng/mL, 45% with a PSA level of 0.2–0.49 ng/mL, 59% with a PSA level of 0.5–0.99 ng/mL, 75% with a PSA level of 1–1.99 ng/mL, and 95% with a PSA level of 2 ng/mL or greater.

The first of these PSMA PET radiopharmaceuticals to receive U.S. Food and Drug Administration approval for prostate cancer evaluation was 68Ga–PSMA-11. In 2021, 18F-DCFPyL was also approved to help identify suspected metastasis or recurrence in patients with prostate cancer. 18F-DCFPyL is becoming increasingly ubiquitous in clinical practice throughout North America. Although either PET/CT or PET/MRI may be used, access to PET/CT is more common at present.

The technique for performing 18F-DCFPyL PET/CT is relatively straightforward. Typically, 333 MBq (9 mCi) of the radiopharmaceutical is administered intravenously. Following an uptake time of 60–120 minutes, images are acquired from the skull vertex to the mid thighs using five to nine bed positions depending on patient height, with 2–3 minutes per bed position. There is no patient preparation required. While many sites use an uptake time of 60 minutes, a longer uptake time (eg, 120 minutes) may be helpful because the conspicuity of prostate cancer lesions is increased. Also, acquiring additional images following the intravenous administration of 10–40 mg of furosemide may be helpful to improve the conspicuity of disease spread to pelvic lymph nodes (4).

Using 18F-DCFPyL PET in the work-up of men with biochemical failure after primary therapy for prostate cancer may result in a change in management plan (5,6). There is evidence supporting the use of 18F-DCFPyL PET in men with castration-sensitive prostate cancer and rising PSA level after prostatectomy and/or radiation therapy when local-regional salvage is being considered (4). There is also evidence supporting the use of 18F-DCFPyL PET in men with potentially oligometastatic castration-sensitive prostate cancer to confirm the disease is not extensive. 18F-DCFPyL PET may be helpful for primary staging in the setting of men with high-risk prostate cancer or in the work-up of men with prostate cancer prior to PSMA therapy (7,8).

Several critical and difficult questions remain unanswered regarding the optimal selection of patients for 18F-DCFPyL PET. For example, although the literature has shown that management frequently changes after 18F-DCFPyL PET, it is unclear if this change has an impact on progression-free survival and/or overall survival. Among other ongoing trials, the PATRON (PSMA PET/CT Guided Intensification of Therapy in Patients at Risk of Advanced Prostate Cancer) study is a phase III prospective multicenter clinical trial (ClinicalTrials.gov identification number: NCT04557501) aiming to determine if changing therapy based on 18F-DCFPyL PET will result in improved progression-free survival and overall survival (9).

Questions also remain regarding the use of 18F-DCFPyL PET versus 18F-fluorodeoxyglucose (FDG) PET in men with prostate cancer. Some sites of metastatic disease are more intensely PSMA-avid than others; some tumor foci may not express PSMA while being 18F-FDG avid. Although our understanding is that expression of PSMA generally increases with greater aggressiveness of prostate adenocarcinoma, tumors can transdifferentiate to a highly aggressive neuroendocrine subtype that can lack expression of PSMA and have high uptake of FDG. The molecular and genomic changes that correlate with our PET biomarkers still require further elucidation.

Depending on the experience of the physician interpreting the PSMA PET scans, the sensitivity and specificity of the interpretation may vary. We know that 18F-DCFPyL (or perhaps a small amount of free 18F for bone lesions) can be taken up at sites of nonaggressive disease such as fibrous dysplasia, Paget disease, hemangiomas, meningiomas, and peripheral nerve sheath tumors, among others. Other malignancies, such as thyroid cancer, lung cancer, and adrenal leiomyosarcoma, may also show uptake of 18F-DCFPyL. Experience with this radiotracer is rapidly growing to help improve our interpretation skills.

In this issue of Radiology, Ulaner et al (10) present data from a prospective trial (ClinicalTrials.gov identification number: NCT04700332) of 184 men, including 92 with newly diagnosed high-risk prostate cancer and 92 with biochemically recurrent prostate cancer with negative findings at conventional imaging (CT and bone scanning) followed by 18F-DCFPyL PET/CT. Suspected distant metastases or recurrences were biopsied and the positive predictive value was calculated.

In total, 23 men with newly diagnosed disease and 37 men with biochemically recurrent disease underwent biopsy. Six of the 23 men with newly diagnosed disease (26%) and four of the 37 men with biochemically recurrent disease (11%) had benign results at biopsy. These false-positive results included four rib lesions, four pelvic bone lesions, and two subcentimeter pelvic nodes or nodules. The biopsy-proven positive predictive value was 74% for distant metastases in men with newly diagnosed high-risk prostate cancer and 89% for recurrent sites in men with biochemical recurrence. Nonmalignant 18F-DCFPyL uptake at PET was most common in the ribs and pelvis, particularly in cases of solitary lesions.

As with most clinical trials, there are several limitations. These include a small sample size, use of only one reader, and not sampling all sites of disease. Furthermore, disease sites sampled were those that were most accessible and safe, which may bias the results. Nonetheless, obtaining histologic proof is an important task, and the authors are to be commended for their work in further validating the reliability of PSMA-targeted PET/CT.

The combination of histologic characterization and the selection of patients with negative findings at conventional imaging contributes toward understanding the value of PSMA-targeted PET/CT in men with prostate cancer. The results of Ulaner et al (10) provide valuable lessons for those of us who perform these complex studies, helping to identify sites of caution for our diagnostic interpretations.

Disclosures of conflicts of interest: K.A.Z. Research grants from the Canadian Cancer Society and Ontario Institute of Cancer Research; consulting fees from Fusion Pharma, GE Healthcare, and Invicro; vice-chair of Finance, SNMMI; Vice-President, ACNM; Vice-Chair, Sylvia Fedoruk Canadian Centre for Nuclear Innovation. P.H.K. Research grant paid to University of Arizona from Blue Earth Diagnostics and GE Healthcare; consulting fees from Amgen, Bayer, Blue Earth Diagnostics, Chimerix, Fusion Pharma, Invicro, and Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eisai, GE Healthcare, and UroToday; payment for expert testimony from Mutual Insurance Company of Arizona; support for attending meeting and/or travel from Bayer, Invicro, and Novartis; payment for participation on a data safety monitoring board or advisory board from Amgen, Bayer, Eisai, and GE Healthcare; unpaid leadership or fiduciary role in other board, society, committee, or advocacy group for Society of Nuclear Medicine and Molecular Imaging and American College of Radiology; part-time employee of Invicro.

References

  • 1. Pienta KJ , Gorin MA , Rowe SP , et al. A Phase 2/3 Prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol 2021;206(1):52–61.
  • 2. Hope TA , Eiber M , Armstrong WR , et al. Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase 3 imaging trial. JAMA Oncol 2021;7(11):1635–1642.
  • 3. Perera M , Papa N , Roberts M , et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: A systematic review and meta-analysis. Eur Urol 2020;77(4):403–417.
  • 4. Shayegan B , Zukotynski K , Bénard F , et al. Canadian Urological Association best practice report: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and PET/magnetic resonance (MR) in prostate cancer. Can Urol Assoc J 2021;15(6):162–172.
  • 5. Rousseau E , Wilson D , Lacroix-Poisson F , et al. A prospective study on 18F-DCFPyL PSMA PET/CT imaging in biochemical recurrence of prostate cancer. J Nucl Med 2019;60(11):1587–1593.
  • 6. Liu W , Zukotynski K , Emmett L , et al. A prospective study of 18F-DCFPyL PSMA PET/CT restaging in recurrent prostate cancer following primary external beam radiotherapy or brachytherapy. Int J Radiat Oncol Biol Phys 2020;106(3):546–555 [Published correction appears in Int J Radiat Oncol Biol Phys 2020;107(2):390.].
  • 7. Sartor O , de Bono J , Chi KN , et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021;385(12):1091–1103.
  • 8. Kuo PH , Benson T , Messmann R , Groaning M. Why We Did What We Did: PSMA-PET/CT Selection Criteria for the VISION Trial. J Nucl Med 2022;63(6):816–818.
  • 9. Ménard C , Young S , Zukotynski K , et al. PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial. BMC Cancer 2022;22(1):251–261.
  • 10. Ulaner GA , Thomsen B , Bassett J , et al. 18F-DCFPyL PET/CT for Initially Diagnosed and Biochemically Recurrent Prostate Cancer: Prospective Trial with Pathologic Confirmation. Radiology 2022;305(2):419–428.

Article History

Received: June 18 2022
Revision requested: June 23 2022
Revision received: June 28 2022
Accepted: June 30 2022
Published online: July 19 2022
Published in print: Nov 2022