Lutetium Lu-177 vipivotide tetraxetan

The molecule has two working parts. One end is a ligand that binds prostate-specific membrane antigen (PSMA), a surface protein that prostate cancer cells often make in high amounts. The other end is a cage-like chelator called DOTA that holds lutetium-177. Once the drug is bound, lutetium-177 gives off beta particles, a short-range form of radiation that damages DNA in the targeted cell and in cells close by, which can lead to cell death. Because it acts mainly where PSMA is present, patients first have a PSMA PET scan to confirm their tumors show the protein. The label lists the salivary glands, kidneys and bone marrow among the normal tissues the drug reaches, which fits its pattern of dry mouth, kidney effects and lowered blood counts.

The evidence comes from large randomized trials in men. In VISION, 831 men whose PSMA-positive metastatic castration-resistant prostate cancer had been treated with androgen-pathway drugs and taxane chemotherapy received the drug plus standard care or standard care alone; median overall survival was 15.3 versus 11.3 months, and imaging-based progression was delayed². PSMAfore, in 468 taxane-naive men, found longer radiographic progression-free survival than switching to another androgen-pathway drug³; the label reports no statistically significant overall-survival difference, with 60% of the comparison group later crossing over to the drug¹. PSMAddition, in 1,144 men with hormone-sensitive metastatic disease, added it to hormone therapy and cut the relative risk of radiographic progression or death by 28%; survival data were still immature^1,4. Grade 3 or worse adverse events were more frequent with the drug in VISION and PSMAddition^2,4.

FDA-approved in 2022 as Pluvicto (Novartis). The current label covers adults with PSMA-positive metastatic prostate cancer, either hormone-sensitive disease (combined with an androgen receptor pathway inhibitor) or disease that has become resistant after such therapy.

Per the FDA label, common effects include fatigue, dry mouth, nausea, and drops in blood counts (lymphocytes, hemoglobin, neutrophils, platelets), plus lab changes in kidney function and electrolytes. Warnings cover severe bone-marrow suppression (deaths have occurred), kidney toxicity, radiation exposure to other people after treatment, possible temporary or permanent male infertility, and fetal harm, so men with partners who could become pregnant are advised to use contraception.

1. FDA label: PluvictoFDA label (DailyMed)
2. Sartor et al., N Engl J Med 2021PubMed
3. Morris et al., Lancet 2024PubMed
4. Tagawa et al., Lancet 2026PubMed