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Open Access 03-02-2025 | Prostate Cancer | Original Article

Biodistribution and dosimetry of [177Lu]Lu-SibuDAB in patients with metastatic castration-resistant prostate cancer

Authors: Philipp Ritt, René Fernández, Cristian Soza-Ried, Heinz Nicolai, Horacio Amaral, Korbinian Krieger, Ana Katrina Mapanao, Amanda Rotger, Konstantin Zhernosekov, Roger Schibli, Cristina Müller, Vasko Kramer

Published in: European Journal of Nuclear Medicine and Molecular Imaging

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Abstract

Purpose

Several prostate-specific membrane antigen (PSMA) radiopharmaceuticals have been used for the treatment of metastatic, castration-resistant prostate cancer (mCRPC). In an attempt to improve the tumour accumulation, new PSMA ligands were developed with an albumin-binding entity to enhance the blood circulation and, hence, tumour accumulation. In preclinical studies, [177Lu]Lu-SibuDAB, a radiopharmaceutical with moderate albumin-binding properties, outperformed [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T. The aim of this study was to evaluate the dosimetry of [177Lu]Lu-SibuDAB in patients diagnosed mCRPC.

Methods

Seventeen patients (median age 72 years, range 63‒83) diagnosed with progressive disease of mCRPC were included in this prospective study after exhausting all available treatment options. They were injected with 5.3 ± 0.5 GBq (mean ± standard deviation) [177Lu]Lu-SibuDAB as a first treatment cycle. Sixteen of these patients underwent sequential whole-body SPECT/CT and activity determination in venous blood samples for dosimetry purposes. Absorbed doses to the salivary glands, liver, spleen, kidneys, and red marrow as well as selected tumour lesions were calculated in OLINDA/EXM™ and compared to published values for previously established PSMA radiopharmaceuticals.

Results

Absorbed dose coefficients (ADC) to tumours (9.9 ± 5.4 Gy/GBq) were about 2-fold higher than those reported for clinically approved PSMA radiopharmaceuticals. ADC to salivary glands, liver, spleen, kidneys and red marrow were higher (0.5 ± 0.2, 0.2 ± 0.05, 0.2 ± 0.1, 1.8 ± 0.6, 0.1 ± 0.04 Gy/GBq, respectively) than for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T, but lower than for [177Lu]Lu-PSMA-ALB-56, a previously investigated long-circulating PSMA radiopharmaceutical. The tumour-to-kidneys, tumour-to-red marrow, tumour-to-salivary glands ADC ratio were 6.6, 102, 33.1. These ratios were comparable to those of [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T for kidneys and red-marrow, but higher for salivary glands.

Conclusion

[177Lu]Lu-SibuDAB showed a prolonged blood circulation time and, hence, a significantly increased absorbed tumour dose, while tumour-to-organ ADC ratios were similar to conventional PSMA radiopharmaceuticals. Further clinical investigations to evaluate the efficacy and safety of [177Lu]Lu-SibuDAB are, thus, warranted.
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Metadata
Title
Biodistribution and dosimetry of [177Lu]Lu-SibuDAB in patients with metastatic castration-resistant prostate cancer
Authors
Philipp Ritt
René Fernández
Cristian Soza-Ried
Heinz Nicolai
Horacio Amaral
Korbinian Krieger
Ana Katrina Mapanao
Amanda Rotger
Konstantin Zhernosekov
Roger Schibli
Cristina Müller
Vasko Kramer
Publication date
03-02-2025
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-025-07102-8