Thrombotic Microangiopathy in Patients Treated with 177Lu-PSMA Combination Therapies

Chan, JC; Carroll, MT; Hitchen, N; Hudson, J; Kostos, LK; Puvanakumar, P; Kranz, S; Tiong, M; Au, L; Buteau, JP; Jackson, P; Azad, AA; Hofman, MS; Ruderman, I; Sandhu, S

Author(s): Chan, JC; Carroll, MT; Hitchen, N; Hudson, J; Kostos, LK; Puvanakumar, P; Kranz, S; Tiong, M; Au, L; Buteau, JP; Jackson, P; Azad, AA; Hofman, MS; Ruderman, I; Sandhu, S;
Details: Publication Year 2026-08-03,Volume 67,Issue #8,Page 1254-1260
Journal Title: Journal of Nuclear Medicine
Publication Type: Research article
Abstract: Over a period of 10 y, our center treated 766 patients with prostate cancer using (177)Lu-PSMA ((177)Lu-PSMA-617 or (177)Lu-PSMA I&T). We report 5 cases of (177)Lu-PSMA-induced thrombotic microangiopathy (TMA). Methods: In this retrospective analysis, we reviewed data from all patients at our center who developed histologically confirmed renal TMA after (177)Lu-PSMA. Clinical, biochemical, and treatment details were summarized descriptively. Results: TMA occurred 9-20 mo after initiating (177)Lu-PSMA therapy. Four patients had a normal baseline estimated glomerular filtration rate (>90 mL/min/1.73 m(2)). All patients developed progressive renal impairment with biopsy-proven chronic TMA. Glomerular endothelial PSMA expression was observed in 2 of 3 cases, suggesting a potential on-target mechanism of injury via an increased cumulative organ dose of (177)Lu-PSMA. The cumulative renal absorbed dose ranged from 38.6 to 65.3 Gy, and the renal absorbed dose per cycle ranged from 5.4 to 12.4 Gy. Two patients received complement inhibition with eculizumab, which improved hematologic features without meaningful renal recovery. Conclusion: (177)Lu-PSMA-associated TMA is a rare but a potentially severe complication of treatment. The contribution of initial versus cumulative renal absorbed dose remains unclear, and early dosimetry may help identify at-risk patients.
Publisher: Society of Nuclear Medicine and Molecular Imaging
Keywords: Aged; Humans; Male; Middle Aged; Dipeptides/adverse effects/therapeutic use; *Heterocyclic Compounds, 1-Ring/adverse effects/therapeutic use; *Lutetium/adverse effects/therapeutic use; *Prostatic Neoplasms/radiotherapy; Radioisotopes/adverse effects/therapeutic use; Retrospective Studies; *Thrombotic Microangiopathies/etiology; *Prostate-Specific Antigen/therapeutic use; 177Lu-PSMA; dosimetry; renal impairment; thrombotic microangiopathy
Department(s): Medical Oncology; Cancer Imaging
Publisher's Version: https://doi.org/10.2967/jnumed.126.272085
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-12 05:40:24

Last Modified: 2026-09-03 12:44:10