177LuPSMA617

177Lu-PSMA-617 (lutetium-177 labeled PSMA-617) is a radioligand therapy used for metastatic castration-resistant prostate cancer. It combines the beta-emitting radionuclide lutetium-177 with PSMA-617, a small molecule that binds to the prostate-specific membrane antigen (PSMA) expressed on most prostate cancer cells. After binding to PSMA, the compound is internalized, delivering targeted radiation to tumor cells and nearby cells, with the intention of inducing DNA damage and cell death while limiting exposure to normal tissues.

Clinically, 177Lu-PSMA-617 is approved in several regions for adults with PSMA-expressing metastatic castration-resistant prostate cancer who have received at least one prior systemic therapy. In the United States, it is marketed as Pluvicto and was approved by the FDA in 2021 based on phase III trial results showing improvements in radiographic progression-free survival and overall survival when added to standard of care in the VISION trial. The European Medicines Agency has granted a similar indication. Treatments are typically given as an intravenous infusion every 6 weeks for up to six cycles; each cycle commonly delivers about 7.4 GBq of activity. Before therapy, PSMA imaging is used to confirm PSMA expression.

Common adverse events include dry mouth (xerostomia), fatigue, nausea, and hematologic toxicity such as anemia or thrombocytopenia. Kidney and liver function are monitored, and dose adjustments or cycle withholding may be necessary for hematologic or organ dysfunction.

Ongoing research explores combinations with other therapies, and evaluation in earlier lines of treatment or other PSMA-targeted radiopharmaceuticals continues to expand the role of this modality in prostate cancer care.