Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto)
High EvidenceAn FDA-approved PSMA-targeted radioligand therapy (brand name Pluvicto) for advanced prostate cancer. It pairs a small PSMA-binding ligand with the radioactive isotope lutetium-177 to deliver radiation directly to cancer cells. In 2026 it gained major traction after the Phase 3 PSMAddition trial showed benefit in earlier, hormone-sensitive disease.
What It Is
Lutetium Lu 177 vipivotide tetraxetan, sold as Pluvicto and known in research as 177Lu-PSMA-617, is a radioligand therapy made by Novartis for men with advanced prostate cancer. It is built from two parts joined together: a small targeting ligand (vipivotide / PSMA-617) that locks onto prostate-specific membrane antigen (PSMA) — a protein found at high levels on most prostate-cancer cells — and the beta-emitting radioactive isotope lutetium-177, attached through a chemical 'cage' (a DOTA-type chelator, the 'tetraxetan' part). When the drug is infused into a vein, the ligand carries the radiation directly to PSMA-positive tumor cells throughout the body, where the lutetium-177 delivers a short-range dose that damages the cancer DNA while largely sparing surrounding tissue. This 'find it, treat it' design is the classic example of a theranostic, because the same PSMA target is first imaged with a companion PSMA-PET scan to confirm a patient is eligible. The U.S. FDA first approved Pluvicto in March 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in men already treated with an androgen-receptor pathway inhibitor (ARPI) and taxane chemotherapy, based on the Phase 3 VISION trial, which showed improved overall survival. In March 2025 the FDA expanded the label to allow use earlier — in PSMA-positive mCRPC after an ARPI but before chemotherapy — supported by the PSMAfore trial. The biggest 2026 development is the Phase 3 PSMAddition trial, which moved Pluvicto into even earlier, hormone-sensitive metastatic disease (mHSPC): adding Pluvicto to standard hormone therapy significantly improved radiographic progression-free survival, with data presented at major 2026 oncology meetings. An important nuance for this site: Pluvicto is technically a radiopharmaceutical, not a classic polypeptide drug — its targeting portion is a small peptide-like (peptidomimetic) molecule rather than a long chain of amino acids. It is included here because it is one of the most prominent 'peptide-targeted' medicines in oncology and a useful illustration of how the word 'peptide' is often stretched in headlines. It is a hospital-administered prescription radiation therapy, not an over-the-counter or research-use peptide.
Regulatory Status
Pluvicto (lutetium Lu 177 vipivotide tetraxetan) was first approved by the U.S. FDA in March 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in patients previously treated with an androgen-receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, based on the Phase 3 VISION trial. In March 2025 the FDA expanded the indication to PSMA-positive mCRPC after an ARPI and before chemotherapy (supported by the PSMAfore trial). In 2026 the Phase 3 PSMAddition trial reported benefit in PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC), supporting further indication expansion. Eligibility requires a positive PSMA-PET scan. It is a prescription radiopharmaceutical administered in specialized centers.
Effective: March 2022 (first approval); expanded March 2025
View FDA SourceWhy Researchers Study It
Pluvicto is studied because it demonstrated that targeted radioligand therapy — delivering radiation directly to cancer cells using a homing molecule — can extend survival in advanced prostate cancer, a disease where options run out quickly once standard hormonal and chemotherapy treatments stop working. Researchers are interested in three questions. First, how early in the disease it should be used: trials have steadily moved it from late-line mCRPC (VISION) to pre-chemotherapy mCRPC (PSMAfore) and now to hormone-sensitive disease (PSMAddition, 2026). Second, how to optimize patient selection and dosing using companion PSMA-PET imaging, the 'theranostic' pairing of a diagnostic scan with a matched therapy. Third, whether the same find-and-treat approach can be applied to other PSMA-positive or antigen-positive cancers and combined with other agents. For this site, it is also a clear teaching example of how the language of 'peptides' overlaps with radiopharmaceuticals: the PSMA-binding ligand behaves like a small targeting peptide, but the finished medicine is a precisely engineered radiation drug, not a wellness or metabolic peptide.
Proposed Mechanisms
- The vipivotide (PSMA-617) ligand binds with high affinity to prostate-specific membrane antigen (PSMA), a protein over-expressed on most prostate-cancer cells
- Once bound, the molecule is internalized by the tumor cell, concentrating the radioactive payload inside the cancer
- The attached lutetium-177 emits short-range beta radiation that breaks tumor-cell DNA, causing cell death while limiting damage to nearby healthy tissue
- Companion PSMA-PET imaging is used first to confirm the tumor is PSMA-positive, matching the diagnostic and therapeutic targets (a theranostic pair)
- By acting throughout the body wherever PSMA-positive cells are found, it provides a systemic, target-directed form of radiation rather than localized external-beam radiation
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Human (Phase 3, pivotal) | VISION trial (NCT03511664): 831 men with PSMA-positive mCRPC previously treated with an ARPI and taxane chemotherapy, randomized to Pluvicto + standard care vs standard care alone | Improved overall survival (median ~15.3 vs 11.3 months; HR ~0.62) and radiographic progression-free survival; basis for the first FDA approval in March 2022 | Source |
| Human (Phase 3) | PSMAfore trial: PSMA-positive mCRPC after an ARPI but before taxane chemotherapy, comparing Pluvicto with a change in ARPI | Improved radiographic progression-free survival, supporting the March 2025 FDA expansion to earlier, pre-chemotherapy use | Source |
| Human (Phase 3, primary results) | PSMAddition trial: PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC), Pluvicto added to standard of care (ADT + ARPI) vs standard of care alone | Statistically significant improvement in radiographic progression-free survival (HR ~0.72, a 28% reduction in risk of progression or death); presented at ASCO 2026 | Source |
| Human (Phase 3, secondary endpoint) | PSMAddition trial PSA analysis (mHSPC), Pluvicto + standard of care vs standard of care alone | 58% lower risk of PSA progression with Pluvicto added to standard care (HR 0.42; 95% CI 0.30–0.59); presented at AUA 2026 | Source |
Commonly Discussed Benefits
Researching Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto)? Track it, set reminders, and keep notes in the free app.
Safety & Cautions
- Pluvicto is a prescription radioligand (radioactive) cancer therapy given by intravenous infusion in specialized centers — it is NOT an over-the-counter or research-use 'peptide'
- It is technically a radiopharmaceutical: its PSMA-targeting part is a small peptide-like molecule, but the finished drug is a radiation medicine, not a classic polypeptide or wellness peptide
- Eligibility requires a positive PSMA-PET scan; it is only for PSMA-positive metastatic prostate cancer and is not a general anti-cancer or anti-aging compound
- Because it is radioactive, treatment requires radiation-safety precautions for the patient, caregivers, and household contacts for a period after each dose
- Common side effects include fatigue, dry mouth, nausea, and low blood counts; the label warns of bone-marrow suppression and kidney effects
- It can cause serious reproductive and embryo-fetal harm and infertility; it is not used in women and is intended only for the approved prostate-cancer setting
- Its 2026 hormone-sensitive (mHSPC) data come from the PSMAddition trial and reflect an expanding role; clinicians determine the right line of therapy for each patient
Comparisons
See how Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto) compares to related peptides:
Calculator Tools
Use our research tools to explore dosing and reconstitution data:
Citations
- [1] FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive mCRPC — Novartis PubMed
- [2] PSMAddition: 177Lu-PSMA-617 Benefits mHSPC Across Disease Burdens (ASCO 2026) — Targeted Oncology PubMed
- [3] Pluvicto demonstrated consistent efficacy across key patient subgroups in mHSPC (PSMAddition, 2026) — Novartis PubMed
Keep researching in the app
- Log Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto) to your private tracker
- Set a dosing reminder
- Compare it side-by-side with your stack
Related Peptides
Thymosin Alpha-1
High EvidenceA thymic peptide approved in some countries for immune modulation, studied for viral infections and cancer adjunct therapy.
SS-31
High EvidenceA mitochondria-targeted peptide FDA-approved as FORZINITY (elamipretide) for Barth syndrome in September 2025 — the first FDA-approved mitochondrial-targeted therapeutic.
Icotrokinra (ICOTYDE)
High EvidenceThe first FDA-approved targeted oral macrocyclic peptide — an IL-23 receptor antagonist for moderate-to-severe plaque psoriasis, marking a new era for oral peptide therapeutics.
Motixafortide (Aphexda)
High EvidenceAn FDA-approved synthetic cyclic peptide and CXCR4 antagonist (brand name Aphexda; research name BL-8040) used together with G-CSF to mobilize blood-forming stem cells for autologous transplant in multiple myeloma. In 2026 it is being actively studied as part of combination immunotherapy for pancreatic cancer.