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

Autor: Zavvar TS; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Hörmann AA; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Konijnenberg M; Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, the Netherlands., Kraihammer M; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Mair C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Kronthaler A; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Joosten L; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands., Laverman P; Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands., Gruber L; Department of Radiology, Medical University of Innsbruck, 6020, Innsbruck, Austria., di Santo G; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Decristoforo C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., Virgolini I; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria., von Guggenberg E; Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria. elisabeth.von-guggenberg@i-med.ac.at.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Dec 07. Date of Electronic Publication: 2024 Dec 07.
DOI: 10.1007/s00259-024-06979-1
Abstrakt: 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 [ 177 Lu]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 [ 177 Lu]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 [ 177 Lu]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 [ 177 Lu]Lu-DOTA-MGS5 in PRRT.
Competing Interests: Declarations. Ethics approval: All animal experiments were approved by the Austrian Ministry of Science (2022–0.351.553) or by the Dutch animal ethics committee (CCD) of the Radboud University and the Nijmegen Medical Centre animal ethics committee (RUDEC) (2020–0007–020). The first dosimetry study in a patient with SCLC was conducted on a named-patient basis. Consent to participate: Written informed consent was obtained from the patient in accordance with the Declaration of Helsinki. Consent to publish: The patient has provided consent for the publication of the data included in this article. Competing interests: EG and AH are listed as an inventor on the European patent application no. 17174973. EG consults Evergreen Theragnostics, Inc. in product development. No other conflict of interest relevant to this article was reported. Clinical trial: Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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