How PSMA-Based Imaging and Therapeutics Can Help Patients With Prostate Cancer
A new review paper explores the possibilities of imaging and therapeutics based around prostate-specific membrane antigen, a protein highly expressed in prostate cancer
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Prostate-specific membrane antigen, or PSMA, is a protein anchored in the cell membrane of prostate epithelial cells that has been found to be strongly upregulated in patients with prostate cancer. For this reason, PSMA is being explored as a target for both imaging diagnostics and targeted radionuclide therapy -- a combination known as PSMA theranostics.
A new review paper looks at the current status and future directions of PSMA theranostics for prostate cancer and its metastases. It summarizes the history of research in PSMA-based imaging -- in particular, PSMA ligands for PET imaging -- and the technique's advantages over conventional methods for the detection of recurrent prostate cancer. The authors of the paper, published in June in the journal Molecular Imaging, then discuss progress made thus far with PSMA-targeted therapy.
“Conventional imaging for prostate cancer includes a bone scan along with a CT scan of the abdomen and pelvis to make sure there is no disease outside of the prostate gland,” said study author Hossein Jadvar, a radiologist at the University of Southern California. “But it has turned out that this method can be inadequate, and sometimes when the conventional imaging is negative, the PSMA PET scan is positive. PSMA-based imaging completely opens new doors to seeing the tumor.”
While the development of PSMA ligands for PET imaging dates back to 2002, the clinical breakthrough in the field occurred with the introduction of gallium-labeled PSMA (68Ga-PSMA-11) PET in 2011. Several studies using this type of PSMA-based imaging demonstrated its high sensitivity and specificity. For instance, 68Ga-PSMA-11 PET has the highest detection probability among all imaging methods for patients with low values of prostate specific antigen -- a protein known as PSA that is found to be elevated in men with prostate cancer.
The reported detection probability for 68Ga-PSMA-11 PET is about 50 percent even at very low PSA levels of less than 0.5 nanograms per milliliter. Jadvar notes that such high sensitivity is particularly beneficial for patients who have already had treatment and are at risk for biochemical recurrence.
“We can use bone scans and CT scans, but those methods usually only find lesions when the patient's PSA is already quite high. If you can detect disease recurrence at low PSA, the chances of a potential cure are higher,” said Jadvar. “PSMA PET is better than anything we’ve had available, which can really change the management of these patients.”
More recently, 18-fluoride-labeled PSMA ligands have been clinically introduced with similarly encouraging results. However, no PSMA-targeted compounds for imaging have been yet approved by the U.S. Food and Drug Administration. But Steven Rowe, a radiologist at Johns Hopkins School of Medicine who was not involved with the paper, believes the agency will approve at least one tracer for imaging hopefully in the near future.
“PSMA-targeted radiotracers have revolutionized our ability to image prostate cancer in a variety of clinical contexts, from newly diagnosed local tumors through biochemical recurrence and advanced metastatic castration-resistant disease,” said Rowe. “A number of sites have made use of 68Ga-labeled agents to investigate many important clinical questions in prostate cancer diagnostic imaging, and the results of those investigations have made PSMA-targeted imaging the clinical standard of care in many places.”
For certain patients with advanced disease, the detection of PSMA on a PET scan could then lead to treatment with PSMA-targeted radioligand therapy, which involves radiopharmaceuticals that specifically bind to a target structure on the tumor. Early retrospective studies are promising, but larger prospective multicenter trials are needed to further determine the treatment's efficacy and toxicity.
“Whether these PSMA-based therapeutics are ever used in the front-line metastatic space or are reserved for those who have failed other lines of therapy remains to be seen,” Rowe said. “The future role of more potent, but also more toxic, therapeutic agents such as those labeled with α-particle emitting radionuclides will also need to be worked out. Therapeutic trials are underway in the United States and the results will ultimately inform the regulatory decisions regarding how these compounds will be used.”