Pluvicto™ (formerly 177Lu-PSMA-617) is a radioligand therapy that was approved by the FDA in March 2022 to treat progressive, PSMA positive metastatic castration-resistant prostate cancer. Pluvicto™ is being further developed by Novartis (originally acquired from the Purdue-startup company Endocyte) for other prostate cancer indications.
Pluvicto™ utilizes a high affinity targeting ligand to direct potent radiotherapy to prostate cancer cells. The specific targeting of this therapy comes from the “ligand” portion of the therapeutic, which is a small molecule designed to bind to Prostate Specific Membrane Antigen, or, PSMA, a protein highly expressed on the cell surface of most prostate cancer cells but absent on most normal cells. The PSMA targeting ligand in Pluvicto™, is chemically attached to a therapeutic radioactive atom called Lutetium-177 (177Lu), which releases an energetic beta particle to precisely deliver cell killing radiation to the site of disease. Unlike traditional external beam radiotherapy, Pluvicto™ is administered as a systemic injection where it can directly target multiple sites of PSMA-positive prostate cancer throughout the body, including the bone and soft tissue, while bypassing the PSMA-negative healthy cells. The expression of PSMA prior to treatment with Pluvicto™ can be determined using whole body PSMA-directed imaging, allowing for personalization of treatment so that the best course of therapy might be selected. It is estimated that approximately 80% of men with metastatic castration-resistant prostate cancer (mCRPC) express PSMA on their cancer cells.
