This study aimed to clarify the renal safety of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC), addressing emerging reports of nephrotoxicity. Methods: We retrospectively analyzed patients with mCRPC from the real-world LUMEN registry who received 3 or more cycles of [177Lu]Lu-PSMA-617. The endpoint was the change in estimated glomerular filtration rate (eGFR) over 24 mo, assessed using linear mixed-effects models. Results: Analysis of 261 patients revealed a modest average decline in eGFR of -0.15 mL/min/1.73 m2 per month (95% CI, -0.25 to -0.05; P = 0.005), translating to -1.80 mL/min/1.73 m2 per year (95% CI, -3.03 to -0.57). The rate of loss accelerated by approximately -0.1 per year per additional gigabecquerel of administered activity (95% CI, -0.18 to -0.01; P = 0.028). Conclusion: [177Lu]Lu-PSMA-617 is associated with a slight long-term average decline in eGFR. Although this is unlikely to be clinically relevant for late-stage mCRPC, the cumulative dose effect warrants careful monitoring in earlier disease stages.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2026 Apr 30 [Epub ahead of print]
Thomas Büttner, Christian Hoffmann, Markus Essler, Florian Gärtner, Barbara Kreppel, Jim Küppers, Manuel Ritter, Leander Fritzsche, Milka Marinova, Philipp Krausewitz
Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; and ., Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; and., Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.