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

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-centre, 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-labelled radioligands in human kidneys. Methods 3D SPECT/computed tomography (CT) imaging of the kidneys was performed after PSMA-RLT in cancer patients with PSMA-positive disease and an adequate glomerular filtration rate (≥50 mL/min). Ten metastatic hormone-sensitive prostate cancer patients (mHSPC) were treated with [¹⁷⁷Lu]Lu-PSMA-617 and 10 advanced salivary gland cancer (SGC) patients were treated with [¹⁷⁷Lu]Lu-PSMA-I&T. SPECT/CT imaging was performed at five timepoints (1 h, 24 h, 48 h, 72 h, and 168 h 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 (independent samples t test; P = 0.010). 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.