Biodistribution and dosimetry of a single dose of albumin-binding ligand [ 177 Lu]Lu-PSMA-ALB-56 in patients with mCRPC
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ORIGINAL ARTICLE
Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC Vasko Kramer 1,2 & René Fernández 1 & Wencke Lehnert 3,4 & Luis David Jiménez-Franco 3 & Cristian Soza-Ried 1 & Elisabeth Eppard 2 & Matias Ceballos 1 & Marian Meckel 5 & Martina Benešová 6,7 & Christoph A. Umbricht 6 & Andreas Kluge 3 & Roger Schibli 6,7 & Konstantin Zhernosekov 5 & Horacio Amaral 1,2 & Cristina Müller 6,7 Received: 21 May 2020 / Accepted: 31 August 2020 # The Author(s) 2020
Abstract Introduction PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMAALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. Results [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. Conclusion Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer. Keywords [177Lu]Lu-PSMA-ALB-56 . PSMA-targeted radionuclide therapy . Albumin-binding PSMA radioligand . mCRPC . Prostate cancer . Dosimetry
This article is part of the Topical Collection on Translational research Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-020-05022-3) contains supplementary material, which is available to authorized users. * Vasko Kramer [email protected]
4
Department of Nuclear Medicine, University Medical Center Hamburg, 20251 Hamburg, Germany
5
ITM Medical Isotopes GmbH, Munich, Germany
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Center for Nuclear Medicine & PET/CT Positronmed, Julio Prado 714, 7501068 Providencia, Santiago, Chile
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Center for Radiopharmaceu
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