Knowledge Hub · ¹⁷⁷Lu-PSMA-617
¹⁷⁷Lu-PSMA-617 is the FDA / EMA-approved theranostic for PSMA-positive metastatic castration-resistant prostate cancer. VISION (2021) established the post-taxane overall survival benefit. PSMAfore (2024) moved the protocol ahead of taxane. The patient is selected on Ga-68 PSMA PET, treated with ¹⁷⁷Lu, then re-imaged on the same PSMA target. This page unpacks the evidence and the dosimetry framework.
Why this matters
VISION (Sartor 2021)
The phase 3 VISION trial randomised 831 men with PSMA-positive mCRPC after taxane + androgen-receptor-pathway-inhibitor (ARPI) therapy. ¹⁷⁷Lu-PSMA-617 plus standard of care extended median overall survival to 15.3 vs 11.3 months (HR 0.62) and median imaging-based PFS to 8.7 vs 3.4 months (HR 0.40). FDA approval followed in March 2022; EMA approval in late 2022.
Based on: Sartor O et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. NEJM 2021; 385:1091-1103 (VISION).
Read source ↗PSMAfore (Morris 2024)
PSMAfore moved ¹⁷⁷Lu-PSMA-617 ahead of taxane in PSMA-positive mCRPC progressing after one ARPI. PRRT extended median radiographic-PFS to 12.0 vs 5.6 months on a second ARPI switch (HR 0.43), with a clinically favourable safety profile vs taxane. PSMA-617 is no longer a post-chemotherapy salvage — it now competes with second-line ARPI.
Based on: Morris MJ et al. Phase 3 PSMAfore trial of ¹⁷⁷Lu-PSMA-617 in pre-taxane mCRPC. Lancet 2024.
Read source ↗PSMA PET patient selection
VISION required Ga-68 PSMA-11 PET/CT showing PSMA-positive disease in at least one target lesion with SUV > liver — a strict eligibility rule. Subsequent dosimetry studies show pre-therapy whole-body SUVmean ≥ 10 correlates with longer PSA-PFS and OS. The PSMA PET is not a screening test; it is the patient-selection decision document.
Based on: Kuo PH et al. ¹⁷⁷Lu-PSMA-617 outcomes by baseline PSMA PET SUV. J Nucl Med 2022; 63:711-718.
Read source ↗Dosimetry and salivary-gland toxicity
PSMA-617 binds PSMA on tumour, salivary gland and lacrimal gland epithelium. Salivary-gland xerostomia is the dose-limiting late toxicity at cumulative protocol doses. Per-cycle Lu-177 SPECT/CT dosimetry estimates tumour and organ-at-risk dose and lets the centre stop at five or six cycles depending on cumulative salivary-gland and kidney exposure.
Based on: Begum NJ et al. Salivary gland dosimetry in ¹⁷⁷Lu-PSMA-617 therapy. EJNMMI 2019; 46:2536-2544.
Read source ↗n.c.a. starting material
PSMA-617 dose per cycle is set by activity (7.4 GBq) not peptide mass. With carrier-added Lu-177 (~600 GBq/mg), the peptide load needed to chelate that activity is ~12 mg per cycle. With SHINE-produced n.c.a. Lu-177 (≥3,000 GBq/mg) it drops to ~2.5 mg — five-fold less cold peptide circulating systemically and competing at the salivary-gland binding sites that drive xerostomia.
Based on: Specific activity claims sourced to the SHINE FDA Drug Master File summary.
Read source ↗EANM PSMA-617 procedural guidance
EANM and SNMMI joint procedural guidance frames the 6-cycle × 7.4 GBq × 6-week protocol, dosimetry expectations, PSMA PET selection thresholds and the labelled-product QC dossier (radiochemical purity ≥ 95 %, endotoxin testing, sterility release). The Indian PSMA-617 SOP plugs into the same framework AERB-licensed centres adopt for theranostics.
Based on: Kratochwil C et al. EANM/SNMMI procedural guidelines for ¹⁷⁷Lu-PSMA-617 therapy. EJNMMI 2023.
Read source ↗VISION + PSMAfore at a glance
15.3 mo
VISION median OS
vs 11.3 mo control
8.7 mo
VISION imaging PFS
vs 3.4 mo control
12.0 mo
PSMAfore rPFS
vs 5.6 mo ARPI switch
6 cycles
7.4 GBq each
6-week intervals
VISION, PSMAfore, EANM/SNMMI procedural guidance and the AERB framework that anchor PSMA-617 in India.
Phase 3 randomised trial of ¹⁷⁷Lu-PSMA-617 in post-taxane mCRPC. FDA / EMA registration trial.
Pre-chemotherapy PSMA-617 vs second-line ARPI — moved PRRT ahead of taxane.
Consensus joint procedural guidance covering selection, protocol, dosimetry and release QC.
Indian framework for Lu-177 sealed / unsealed source import and theranostic-facility licensing.