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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-03-2021 | Prostate Cancer | Original Article

Biodistribution and dosimetry of a single dose of albumin-binding ligand [¹⁷⁷Lu]Lu-PSMA-ALB-56 in patients with mCRPC

Authors: Vasko Kramer, René Fernández, Wencke Lehnert, Luis David Jiménez-Franco, Cristian Soza-Ried, Elisabeth Eppard, Matias Ceballos, Marian Meckel, Martina Benešová, Christoph A. Umbricht, Andreas Kluge, Roger Schibli, Konstantin Zhernosekov, Horacio Amaral, Cristina Müller

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2021

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-PSMA-ALB-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.

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Title: Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC
Authors: Vasko Kramer
René Fernández
Wencke Lehnert
Luis David Jiménez-Franco
Cristian Soza-Ried
Elisabeth Eppard
Matias Ceballos
Marian Meckel
Martina Benešová
Christoph A. Umbricht
Andreas Kluge
Roger Schibli
Konstantin Zhernosekov
Horacio Amaral
Cristina Müller
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Radionuclide Therapy
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-05022-3

At a glance: The STEP trials

Springer Medicine

Biodistribution and dosimetry of a single dose of albumin-binding ligand [¹⁷⁷Lu]Lu-PSMA-ALB-56 in patients with mCRPC

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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