PSMA radioligand therapy using 177Lu-PSMA I&T and 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: comparison of safety, biodistribution and dosimetry

Ziel/Aim To determine the safety, kinetics and dosimetry of 177 Lu labeled prostate specific membrane antigen (PSMA) small molecules 177 Lu-PSMA I&T and 177 Lu-PSMA-617 in a large cohort with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methodik/Methods 138 pts (mean age, 70±9 y; range 46-90) with progressive mCRPC, PSMA expression verified by 68 Ga-PSMA-11 PET/CT, underwent PRLT. 51 pts received 6.1±1.0 GBq (range 3.4-7.6) 177 Lu-PSMA I&T and 87 pts received 6.5±1.1 GBq (range 3.5-9.0) 177 Lu-PSMA-617. Dosimetry was identically performed in all patients. Mean absorbed doses (MAD) were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded to CTCAEv 5.0. Ergebnisse/Results Whole-body half-lives were shorter for 177 Lu-PSMA I&T (35 h) compared to 177 Lu-PSMA-617 (42 h). Mean whole-body dose of 177 Lu-PSMA-617 was higher as compared to 177 Lu-PSMA I&T (0.04 vs. 0.03 Gy/GBq, p<0.00001). The renal dose of 177 Lu-PSMA-617 was despite higher half life, lower than for 177 Lu-PSMA I&T (0.77 vs 0.92 Gy/GBq, p=0.0015). Both demonstrated comparable doses to parotid glands (0.5 Gy/GBq, p=0.26603). For normal organs, lacrimal glands exhibited the highest MAD of 5.1 Gy/GBq and 3.7 Gy/GBq for 177 Lu-PSMA-617 and 177 Lu-PSMA I&T. Metastases exhibited higher initial uptake using 177 Lu-PSMA I&T and shorter tumor half-life (p<0.00001). Tumor MAD were comparable for both (p=0.96257). All patients tolerated therapy without adverse effects only a small statistically significant reduction in Hb, LPK counts and TPK counts after 177 Lu-PSMA-617 and 177 Lu-PSMA I&T not needing clinical intervention. No nephrotoxicity was observed. Schlussfolgerungen/Conclusions Both 177 Lu-PSMA I&T and 177 Lu-PSMA-617 PRLT were safe in mCRPC patients. Highest MAD amongst healthy organs were in lacrimal and parotid glands with no sequele. 177 Lu-PSMA-617 demonstrated higher whole-body and lacrimal glands MAD but lower renal doses as compared to 177 Lu-PSMA-I&T. Tumor MAD were comparable for both. There was a large inter-patient variability of dosimetry parameters; individual dosimetry seems favorable for personalized PRLT. Publication History Article published online: 30 March 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany