Dosimetry and safety of 177Lu-PSMA radioligand therapy among patients with a single kidney as compared to patients with both kidneys with or without baseline renal insufficiency (RI)

Objectives: Prostate-specific membrane antigen (PSMA) expression in the apical epithelium of the proximal tubules and high post-therapy uptake in kidneys after PSMA radioligand therapy (PRLT) raise concern about the tolerability and potential nephrotoxicity, especially in patients with already known renal insufficiency (RI), as well as potential increased background radiation dose. The aim of this study was to compare dosimetry and safety of PRLT using 177Lu-PSMA-617 among prostate cancer patients with a single functioning kidney, patients with both kidneys but already known RI before PRLT, and patients with both kidneys without RI before PRLT. Methods: A total of 80 patients (14 patients with a single functioning kidney, 13 patients with both kidneys, but already known RI before PRLT, and 53 patients with both kidneys and normal baseline renal function) were included in this study and retrospectively analyzed. All patients had PSMA-positive metastases confirmed on 68Ga-PSMA PET/CT, had received at least 2 cycles of 177Lu-PSMA-617 radioligand therapy, and underwent both, post-therapy planar whole-body scintigraphy and SPECT/CT following dosimetry procedure. An established protocol practicable in our daily clinical routine was used for dosimetry calculation based on the MIRD-scheme. Mean absorbed doses was estimated using the software OLINDA 2.0. All parameters of renal and hematological toxicity profile were prospectively documented in a structured database and analyzed prior to each PRLT cycle and in follow-up (restaging was performed regularly until death). Treatment-related adverse events were graded according to the CTCAE v.5.0. Results: In patients with a single functioning kidney, the mean injected activity per cycle was 6.39 ± 1.05 (range, 3.9 - 8.1) GBq. Calculated radiation-absorbed doses of the kidney were 0.81 ± 0.32 Gy/GBq. The absolute doses to whole-body were 0.058 ± 0.027 Gy/GBq. In patients with both functioning kidneys, the mean injected activity per cycle was 6.5 ± 1.1 (range, 3.5 - 9.0) GBq. The dose estimations for 177Lu-PSMA-617 revealed a mean absorbed dose of 0.8 Gy/GBq for kidneys with effective half-life of 40 hours. The absolute doses to whole-body were 0.04 Gy/GBq with effective half-life of 42 hours. In patients with a single functioning kidney, renal function (CTCAE G0 : G1: G2) were 50% : 29% : 21% before PRLT, 50% : 43% : 7% after the first cycle of PRLT, 50% : 36% : 14% after the second cycle of PRLT. In patients with both k