PSMAdirected

PSMAdirected, commonly written PSMA-directed, refers to medical strategies that target the prostate-specific membrane antigen (PSMA) for the diagnosis and treatment of prostate cancer. The term covers PSMA-directed imaging used for detection and staging, and PSMA-targeted radioligand therapy that delivers radiation to PSMA-expressing cells. PSMA is commonly expressed in prostate cancer, especially in advanced disease, making it a useful molecular target.

PSMA-directed diagnostics use PET imaging with PSMA ligands such as Ga-68-PSMA-11 or F-18 PSMA tracers. These scans improve lesion detection, inform staging, and help select patients for PSMA-directed therapies.

PSMA-directed radioligand therapy employs therapeutic radiopharmaceuticals that bind PSMA and emit cytotoxic radiation, most notably Lu-177–PSMA-617. Treatments are given in several cycles spaced weeks apart. In metastatic castration-resistant prostate cancer, PSMA-directed therapy has shown improvements in progression-free and overall survival in trials and is approved in many regions. Common side effects include dry mouth, mild hematologic toxicity, fatigue, and nausea; kidney and salivary gland radiation exposure can occur.

Regulatory status varies by country. In the United States, Lu-177–PSMA-617 was approved for adults with PSMA-PET–positive metastatic castration-resistant prostate cancer after at least one prior therapy. Guidelines generally recognize PSMA-directed therapy as a care option for selected advanced cases.

Research continues into earlier-line use, combination therapies, and alternative isotopes such as actinium-225. Limitations include heterogeneous PSMA expression, potential resistance, and non-response, underscoring the need for biomarkers and careful patient selection.

See also PSMA PET, radioligand therapy, prostate cancer.