PSMA617

PSMA-617 refers to a small-molecule ligand that binds to PSMA, a transmembrane glycoprotein overexpressed in many prostate cancers. The compound contains a urea-based PSMA-inhibitor moiety linked to a chelator such as DOTA, enabling radiolabeling with therapeutic radionuclides. When labeled with lutetium-177, the resulting radioligand Lutetium-177-PSMA-617 delivers targeted beta radiation to PSMA-expressing tumor cells, causing DNA damage and cell death while largely sparing surrounding tissue. The same PSMA-617 scaffold can be labeled with other radionuclides, including actinium-225, for alpha therapy, and PSMA-617-based tracers are used in diagnostic imaging with gallium-68 for PSMA PET.

In clinical use, Lu-177-PSMA-617 has been evaluated as part of a theranostic approach for metastatic castration-resistant prostate cancer (mCRPC). In the United States, the FDA approved Lu-177-PSMA-617 in 2021 for adults with PSMA-PET–positive mCRPC following at least one line of taxane-based chemotherapy, based on the VISION trial demonstrating overall survival benefit. The typical regimen is 7.4 GBq (200 mCi) IV every six weeks for up to six cycles, with treatment guided by PSMA PET imaging and hematologic reserve. Common side effects include dry mouth, nausea, fatigue, mild renal and hepatic function impact, and hematologic toxicity such as anemia or thrombocytopenia. It is marketed under the name Pluvicto by Novartis. Ongoing research explores combination strategies, use in other settings, and alpha-emitting isotopes such as 225Ac-PSMA-617.