What it is
Vipivotide tetraxetan is the targeting molecule inside Pluvicto, and it is not a classic peptide. The label calls it "a PSMA-binding ligand bound to a DOTA chelator radiolabeled with lutetium-177." Read piece by piece from the label's chemical name, it has three parts: a binding motif made of glutamate and lysine joined by a urea bond (not a peptide bond), a linker of 2-naphthylalanine — an amino acid not found in proteins — and a cyclohexane ring, and a DOTA cage that holds the radioactive metal. That mix of amino-acid building blocks and non-peptide chemistry is what "peptidomimetic" means; the reading is ours, labelled as such. Formula C49H68(177Lu)N9O16, molecular mass 1,216 g/mol.
Its research name is PSMA-617. Loaded with lutetium-177 it becomes the finished drug, lutetium Lu 177 vipivotide tetraxetan, sold as Pluvicto. The library's other radioligand, dotatate, works the same way but its targeting part is a true eight-residue peptide.
How it works
PSMA (prostate-specific membrane antigen) is a protein that sits in the membrane of most prostate cancer cells. The glutamate–urea–lysine motif binds it, the drug is drawn into the cell, and lutetium-177 does the damage: it decays with a half-life of 6.647 days, emitting beta particles with a maximum energy of 498 keV that break DNA in the bound cell "as well as in surrounding cells" (label). The radiation is the medicine; the ligand is the delivery address. This is why a PSMA PET scan comes first — men in every trial had to show uptake on a gallium Ga 68 gozetotide scan greater than in normal liver.
What the label's trials show
| Trial | Who | Comparison | Main result |
|---|---|---|---|
| VISION (NCT03511664) | 831 men after hormone drugs and taxane chemotherapy | Pluvicto + standard care vs standard care (2:1) | Median survival 15.3 vs 11.3 months, HR 0.62 (0.52–0.74); response in 49% vs 1.6% of men with measurable disease |
| PSMAfore (NCT04689828) | 468 men after one hormone drug, before chemotherapy | Pluvicto vs a change of hormone drug | Progression-free survival 9.3 vs 5.6 months, HR 0.41; survival 24.5 vs 23.1 months, not significant (HR 0.91) |
| PSMAddition (NCT04720157) | 1,144 men before hormone therapy had failed | Pluvicto + hormone drug vs hormone drug alone | Progression or death 24% vs 30%, HR 0.72 (0.58–0.90); survival data immature (25% had died) |
All three were open-label — patients and doctors knew who received what — with progression read by a blinded central review. Two things the table does not show on its own: in VISION the label says the progression result was hard to size "due to a high degree of censoring from early drop out in the control arm," and in PSMAfore 141 of 234 men (60%) in the control arm crossed over to Pluvicto after progressing, which blurs any survival comparison.
Safety
In the pooled safety population of the three trials (1,320 men) the most common reactions were blood-count falls — lymphocytes 86%, haemoglobin 68%, neutrophils 35%, platelets 33% — plus fatigue (51%), dry mouth (46%) and nausea (35%) (label). The warnings are radiation exposure to others, myelosuppression, kidney toxicity, harm to a fetus and infertility; the label asks treating teams to monitor blood counts and kidney function and to adjust or stop doses by severity. Dose and schedule are set by the nuclear-medicine team.
Where it stands
- Approved in the US on 2022-03-23 (Pluvicto, NDA 215833, Novartis) for men after hormone drugs and chemotherapy; extended by efficacy supplements on 2025-03-28 (before chemotherapy) and 2026-07-31 (with a hormone drug, before hormone therapy has failed) (Drugs@FDA, data 2026-10-16). Label effective 2026-08-12.
- Research record: PubMed indexes 538 records, 17 tagged as randomised controlled trials; ClinicalTrials.gov lists 100 studies naming 177Lu-PSMA-617 (2026-10-17).
Related reading
The same deliver-a-radioactive-atom design, built on a true peptide, is dotatate, the somatostatin-receptor radioligand. Pluvicto is given with drugs that act on the hormone axis such as the GnRH analogue leuprolide. For why some peptide-like drugs are not counted as peptides, see what counts as a peptide chain.