Detecting Metastases Using Prostate Enzyme During SPECT Imaging

Metastatic prostate cancer cells, no matter where they hide, still express some of the same signaling as normal prostate cells; in some cases even more so, as with the prostate-specific membrane antigen (PSMA) enzyme. Being able to control this enzyme could help in the development of a new platform for prostate cancer detection, staging, treatment, and post-treatment monitoring.

Researchers reported their findings at the 60th Society of Nuclear Medicine and Molecular Imaging’s 2013 annual meeting, held June 8-12, 2013, in Vancouver (BC, Canada). “There are currently no ideal imaging techniques in clinical practice that are specific to prostate cancer,” said Shankar Vallabhajosula, PhD, a professor of radiochemistry from the department of radiology at Weill Cornell Medical College (New York, NY, USA). “We regularly use bone scans to image metastatic prostate cancer, but bone scans are not specific for these tumors. This study focuses on a novel imaging agent that binds to PSMA, an enzyme expressed by prostate epithelial cells. We don’t really know what its role is in prostate cancer, but imaging agents using either anti-PSMA antibodies or small molecules that specifically bind to the enzymatic site of PSMA are capable of detecting both primary prostate cancer cells and secondary metastases in other organs. This development could lead to highly specific prostate cancer imaging and potentially optimal care for patients.”

In two early phase I studies involving PSMA, also known as glutamate carboxypeptidase II(GCPII) or NAAG peptidase, researchers evaluated an imaging agent comprising a small molecule of amino acids, called MIP-1404 (based on glutamate-urea-glutamate pharmacophore) radiolabeled with technetium-99m (Tc-99m), which is detectable by single photon emission computed tomography (SPECT) that provides functional imaging of prostate cancer. Tc-99m MIP-1404 SPECT imaging produces a scan or a map of where this novel agent is bound to PSMA enzyme in metastatic prostate tumors throughout the body. Tc-99m MIP-1404 represents a much more marketable and clinically viable agent because it is easy to make and has a faster rate of distribution throughout the body and clearance from the body, unlike imaging agents based on anti-PSMA monoclonal antibodies that were unwieldy and require long wait times to obtain images.

The study findings revealed that Tc-99m MIP-1404 was well distributed and ready for imaging as soon as one hour after injection for localization of cancer lesions in bone and lymph nodes. In a majority of cases, Tc-99m MIP-1404 pointed out more lesions than standard bone imaging. “This agent could one day be a molecular imaging biomarker not just for screening patients with prostate cancer and metastases but also for monitoring their response to subsequent treatment,” said Dr. Vallabhajosula. “In time, it could also be formulated as a therapeutic radioactive drug.”

Tc-99m MIP-1404, developed by Molecular Insight Pharmaceuticals, Inc. (Cambridge, MA, USA), a wholly owned subsidiary of Progenics Pharmaceuticals, Inc., is now in a phase II international multicenter study. Additional research and US Food and Drug Administration (FDA) approval are required, according to the scientists, before this radiopharmaceutical agent could be introduced to general clinical practice for prostate cancer imaging.

Related Links:
Weill Cornell Medical College
Molecular Insight Pharmaceuticals