BERKELEY, CA (UroToday.com) - Conventional PET scans rely on the fact that many tumors accumulate radio-labeled glucose, fluorodeoxyglucose (18F) or FDG, as a means of detecting occult cancer. However, prostate cancer is rather poor at accumulating glucose analogs, and the detection of prostate cancer by PET imaging has been modest at best. CMS has recognized this shortcoming, and as a result, Medicare does not cover prostate cancer as an indication for PET imaging.
Efforts to enhance prostate cancer detection have focused extensively on targeting PSMA, as this cell surface marker is present in the vast majority of high-risk prostate cancer cells and is quite specifically up-regulated in prostate cancer cells compared to benign prostatic epithelium. The first attempt to specifically target prostate-specific membrane antigen (PSMA) for imaging was based on the very antibody from which PSMA was initially characterized (a mouse monoclonal antibody called 7E11). The antibody was conjugated to a radioactive tracer and then injected intravenously into patients in the ProstaScint® scan. Unfortunately, at the time the ProstaScint® was conceived, it was not known that 7E11 targeted an intracellular epitope—which would not be exposed in a viable tumor cells. It was thought that the relatively low signal from the ProstaScint® scan was because the scan was focusing on dead or dying prostate cancer cells, but not active disease. Subsequent generations of this strategy focused on an antibody targeting the extracellular face of PSMA (J591), with improved success. However, the field has shifted quite dramatically away from antibody-mediated imaging and its inherent problems and focused on small molecules which target the active site of PSMA.
This paper gives a very concise but detailed review of the development of small molecule inhibitors of PSMA, discussing the nuances of each family of inhibitors. These new inhibitors are becoming increasingly developed for clinical translation with PET/SPECT imaging, potentially allowing the urologic surgeon to visualize individual foci within the prostate. Such information would be immensely valuable for the surgeon for surgical planning, or for active surveillance programs as a means of risk stratification. Importantly, these new small molecule inhibitors of PSMA have been recently conjugated to near-infrared fluorophores, allowing real-time imaging for surgical extirpation. In principle, the development of real-time near infrared imaging of prostate cancer potentially could enable a robotic surgeon to visualize cancer at the edges of resection to prevent positive margins. In addition, it might allow surgeons to focus the pelvic lymph node dissection to suspicious nodes only, hence decreasing the morbidity of lymphadenectomy while increasing the diagnostic and potentially therapeutic impact.
Written by:
Ron Rodriguez, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Henry B. and Edna Smith Dielmann Memorial Chair in Urologic Science
Professor and Chairman, Department of Urology
University of Texas Health Science Center San Antonio
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PET imaging in prostate cancer: Focus on prostate-specific membrane antigen - Abstract
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