Lutetium-177 PSMA-617
Oncology / Prostate CancerAlso known as: Pluvicto, 177Lu-PSMA-617, Lu-PSMA, Lutetium-177 vipivotide tetraxetan
Mechanism
Pluvicto (Lu-177 PSMA-617) is a targeted radioactive treatment for advanced prostate cancer. It combines a small molecule that binds PSMA (a protein highly expressed on prostate cancer cells) with a radioactive isotope (lutetium-177) that destroys cancer cells with beta radiation. The targeting molecule delivers the radiation directly to cancer cells while sparing most healthy tissue.
Technical detail
Lu-177 PSMA-617 consists of a PSMA-binding peptidomimetic ligand (glutamate-urea-lysine motif targeting the enzymatic site of PSMA/FOLH1/GCP-II) conjugated via a DOTA chelator to lutetium-177 (beta-emitting radioisotope, half-life 6.7 days, max beta energy 0.497 MeV, tissue penetration ~2mm). Upon binding PSMA on prostate cancer cells, the complex is internalized via clathrin-mediated endocytosis. Lu-177 beta emissions cause DNA double-strand breaks within the target cell and adjacent cells (crossfire effect). The VISION trial showed improved radiographic PFS and OS in mCRPC. PSMA PET imaging is required to confirm PSMA expression prior to treatment.
Evidence
- strong
Fizazi K et al. (2023) — The Lancet Oncology — PMID: 37269841
Follow-up VISION analysis reported better health-related quality of life and pain outcomes with 177Lu-PSMA-617 plus standard care versus standard care alone, supporting patient-centered benefit in addition to survival gains.
- strong
Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.
Sartor O et al. (2021) — The New England Journal of Medicine — PMID: 34161051
VISION phase III trial showed 177Lu-PSMA-617 plus standard care improved imaging-based progression-free survival (8.7 vs 3.4 months; HR 0.40) and overall survival (15.3 vs 11.3 months; HR 0.62) versus standard care alone in metastatic castration-resistant prostate cancer.