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European Journal of Nuclear Medicine and Molecular Imaging
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Open Access 07-12-2024 | Radionuclide Therapy | Original Article

Radiopharmaceutical formulation and preliminary clinical dosimetry of [177Lu]Lu-DOTA-MGS5 for application in peptide receptor radionuclide therapy

Authors: Taraneh Sadat Zavvar, Anton Amadeus Hörmann, Mark Konijnenberg, Martin Kraihammer, Christian Mair, Ariane Kronthaler, Lieke Joosten, Peter Laverman, Leonhard Gruber, Gianpaolo di Santo, Clemens Decristoforo, Irene Virgolini, Elisabeth von Guggenberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2025

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Abstract

Purpose

Radiolabelled minigastrin (MG) analogues targeting the cholecystokinin-2 receptor (CCK2R) have proven to be a promising approach for peptide receptor radionuclide therapy (PRRT). In this study, we report on the radiopharmaceutical development and standardization of the preparation of [177Lu]Lu-DOTA-MGS5 using an automated synthesis module. Furthermore, we present the preclinical tests required to move forward towards a first therapeutic clinical trial as well as preliminary clinical dosimetry data.

Methods

Five individual batches of [177Lu]Lu-DOTA-MGS5 were synthesized and analysed according to predefined quality control specifications. Cell-based experiments and biodistribution studies were performed to evaluate the specific receptor binding and tumour uptake of the radiopharmaceutical formulation. A preclinical dosimetry study was carried out in tumour xenografted mice and a first dosimetry study was performed in a patient with small cell lung cancer.

Results

The automated cassette-based production of [177Lu]Lu-DOTA-MGS5 resulted in a product with high radiochemical purity of > 98% and high stability. The new radiopharmaceutical showed a favourable biodistribution profile in A431-CCK2R xenografted BALB/c nude mice. Pharmacokinetic data obtained in mice and dosimetry extrapolation demonstrated the feasibility of PRRT. In the preliminary patient-specific dosimetry study, a low risk of toxicity was shown and a mean absorbed dose of 12.5 ± 10.2 (1.2–28) Gy/GBq was calculated for delineable tumour lesions.

Conclusion

The radiopharmaceutical development and the preclinical/clinical results support the initiation of a first clinical trial to evaluate the therapeutic potential of [177Lu]Lu-DOTA-MGS5 in PRRT.
Appendix
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Metadata
Title
Radiopharmaceutical formulation and preliminary clinical dosimetry of [177Lu]Lu-DOTA-MGS5 for application in peptide receptor radionuclide therapy
Authors
Taraneh Sadat Zavvar
Anton Amadeus Hörmann
Mark Konijnenberg
Martin Kraihammer
Christian Mair
Ariane Kronthaler
Lieke Joosten
Peter Laverman
Leonhard Gruber
Gianpaolo di Santo
Clemens Decristoforo
Irene Virgolini
Elisabeth von Guggenberg
Publication date
07-12-2024
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2025
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-024-06979-1

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