Lutetium (177Lu) vipivotide tetraxetan — Drug Monograph
Brand names: Pluvicto
Drug class: Other
Mechanism of Action
Radioligand therapy consisting of a PSMA (prostate-specific membrane antigen)-targeting small molecule ligand (vipivotide) conjugated to the beta-emitting radioisotope lutetium-177 (¹⁷⁷Lu) via a PSMA-617 chelating scaffold. After IV administration, the ligand binds PSMA expressed on prostate cancer cells with high affinity and is internalized, delivering targeted ionizing beta radiation (tissue penetration ~1 mm, ~7-day physical half-life) directly to tumor cells and adjacent microenvironment while limiting systemic exposure.
FDA Indications
- PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in adults who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy (FDA approved March 2022; VISION trial: OS HR 0.62, 38% reduction in death; rPFS HR 0.40, 60% reduction in radiographic progression or death)
Common Side Effects
- Fatigue (43%)
- Dry mouth/xerostomia (39% — salivary gland radiation)
- Nausea (35%)
- Anemia (32%)
- Thrombocytopenia (20%)
- Neutropenia (18%)
- Diarrhea (21%)
- Vomiting (17%)
- Decreased appetite (20%)
- Urinary tract infection
Clinical Pearl
Lutetium-177 PSMA-617 (Pluvicto) is a landmark radioligand therapy that demonstrated survival benefit in mCRPC post-ARPI and taxane (VISION: OS HR 0.62). Administration is restricted to certified nuclear medicine centers. The PSMA PET/CT is mandatory for patient selection, and xerostomia from salivary gland irradiation affects ~39% of patients and can be partially mitigated by salivary gland protective strategies. Patient education about radiation safety precautions for household contacts is…