Kidney absorbed radiation doses for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T determined by 3D clinical dosimetry

Abstract Purpose: For prostate-specific membrane antigen directed radioligand therapy (PSMA-RLT), [177Lu]Lu‑PSMA‑617 and [177Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [177Lu]Lu-PSMA-I&T compared to [177Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity. We performed two single center, prospective dosimetry studies with either [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T, using an identical dosimetry protocol. We evaluated the absorbed doses of both 177Lu labeled radioligands in human kidneys.Methods: 3D SPECT/CT imaging of the kidneys was performed after PSMA-RLT in cancer patients with PSMA-positive disease and an adequate glomerular filtration rate (GFR) (≥50 mL/min). Ten metastatic hormone-sensitive prostate cancer patients (mHSPC) were treated with [177Lu]Lu‑PSMA‑617 and ten advanced salivary gland cancer (SGC) patients were treated with [177Lu]Lu-PSMA-I&T. SPECT/CT imaging was performed at 5 time points (1h, 24h, 48h, 72h, and 168h post injection). In mHSPC patients SPECT/CT imaging was performed after cycles 1 and 2 (cumulative activity: 9 GBq) and in SGC patients only after cycle 1 (activity: 7.4 GBq). Kidney absorbed dose was calculated using organ-based dosimetry. Results: The median kidney absorbed dose was 0.49 Gy/GBq (range: 0.34-0.66) and 0.73 Gy/GBq (range: 0.42-1.31) for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T, respectively (Wilcoxon-Mann-Whitney; p=0.002). Conclusion: This study shows that the kidney absorbed dose for [177Lu]Lu-PSMA-617 and [177Lu]Lu‑PSMA-I&T differs, with a ~1.5x higher median kidney absorbed dose for [177Lu]Lu-PSMA-I&T. This difference in the clinical setting is considerably smaller than observed in preclinical studies and may not hamper treatments with [177Lu]Lu-PSMA-I&T.