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

Maike J.M. Uijen, Bastiaan M. Privé, Carla M.L. Van Herpen, Harm Westdorp, Willemijn A. Van Gemert, Maarten De Bakker, Martin Gotthardt, Mark W. Konijnenberg, Steffie M.B. Peters, James Nagarajah*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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-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.

Original languageEnglish
Pages (from-to)270-275
Number of pages6
JournalNuclear Medicine Communications
Volume44
Issue number4
DOIs
Publication statusPublished - 1 Apr 2023

Bibliographical note

Funding Information:
This work was supported by the Dutch Cancer Society (KWF), the Dutch Prostate cancer foundation, and the Radboud Oncology Foundation.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

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