Applications of PSMA-PET in tumors other than prostate cancer

Prostate-specific membrane antigen (PSMA) is a transmembrane type II glycoprotein with the catalytic site positioned in the extracellular domain of the molecule. Following its discovery in 1987, it was cloned and subsequently identified in human tissues. While PSMA is expressed in normal prostatic parenchyma, expression levels are higher in benign epithelium and even higher in adenocarcinoma. Initially, anti-PSMA monoclonal antibodies were instrumental in establishing that overexpression of PSMA was not confined to prostate tissue or prostate cancer. Rather, a number of studies reported its expression in a number of non-prostatic tumors, including breast, lung, renal, colon, urinary bladder, nervous systems, gastric and other malignancies. The differential in expression levels plus accessibility to the catalytic site via a parenteral route of administration have led to the development of a number of small and highly specific PSMA-targeting radiopharmaceuticals. Because of the many advantages of radiochemical synthesis with positron-emitting radionuclides and imaging capabilities of Positron Emission Tomography (PET), the two technologies have been used to evaluate a number of promising 18F- and 68Ga-based molecular imaging agents. While there are a number of small PSMA-targeting molecules under development, the three that have advanced the most in the clinic are: 68Ga-PSMA-11, 18F-DCFPyL and 18F-PSMA-1007. The FDA recently granted NDAs to UCLA and UCSF for 68Ga-PSMA-11 production, and Lantheus Holdings, Inc. for 18F-DCFPyL for PET imaging of men with prostate cancer. Other groups are developing radiopharmaceuticals conjugated with both imaging (18F) and therapeutic radionuclides (177Lu, 188Re, 225Ac) for use in theranostic settings. Finally, efforts are underway to provide greater access, cost efficiency and productivity to these PSMA-PET technologies by automating the production process. The convergence of our increasing understanding of PSMA biology and the technological advancements to allow more widespread use of PSMA-PET will ultimately have positive benefits for treatment management of cancer patients.