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Article

Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial

Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria
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Author to whom correspondence should be addressed.
Academic Editor: Gerald Reischl
Pharmaceuticals 2021, 14(6), 575; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060575
Received: 20 May 2021 / Revised: 11 June 2021 / Accepted: 12 June 2021 / Published: 16 June 2021
The new minigastrin analog DOTA-MGS5 is a promising new candidate for targeting cholecystokinin-2 receptor (CCK2R)-expressing tumors. To enable the clinical translation of PET/CT imaging using 68Ga-labeled DOTA-MGS5, different quality and safety aspects need to be considered to comply with the regulatory framework for clinical trial application. The preparation of the radiopharmaceutical was established using a cassette-based automated synthesis unit. Product specifications, including analytical procedures and acceptance criteria, were adopted from Ph. Eur. monographs for other 68Ga-labeled radiopharmaceuticals. Non-clinical studies included receptor affinity and cell uptake studies using two different CCK2R-expressing cell lines, as well as pharmacokinetic biodistribution studies in BALB/c mice for dosimetry calculations and toxicological studies in Wistar rats. The produced masterbatches fulfilled the defined acceptance criteria. DOTA-MGS5, with confirmed affinity to the CCK2R, showed a high specific cell uptake and no interaction with other receptors in vitro when radiolabeled with gallium-68. Favorable in vivo properties were observed in biodistribution and dosimetry studies. An effective dose of ~0.01 mSv/MBq was estimated for humans utilizing OLINDA/EXM software. A maximum peptide dose of 50 µg was established for the initial clinical dose based on the toxicity study in rats. The standardized production of [68Ga]Ga-DOTA-MGS5 using an automated synthesis module and the performed non-clinical safety studies support a first exploratory clinical trial with this new PET imaging agent. View Full-Text
Keywords: cholecystokinin-2 receptor; minigastrin; molecular imaging; radiometals; clinical trial; automated synthesis cholecystokinin-2 receptor; minigastrin; molecular imaging; radiometals; clinical trial; automated synthesis
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MDPI and ACS Style

Hörmann, A.A.; Klingler, M.; Rangger, C.; Mair, C.; Decristoforo, C.; Uprimny, C.; Virgolini, I.J.; von Guggenberg, E. Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial. Pharmaceuticals 2021, 14, 575. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060575

AMA Style

Hörmann AA, Klingler M, Rangger C, Mair C, Decristoforo C, Uprimny C, Virgolini IJ, von Guggenberg E. Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial. Pharmaceuticals. 2021; 14(6):575. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060575

Chicago/Turabian Style

Hörmann, Anton A., Maximilian Klingler, Christine Rangger, Christian Mair, Clemens Decristoforo, Christian Uprimny, Irene J. Virgolini, and Elisabeth von Guggenberg. 2021. "Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial" Pharmaceuticals 14, no. 6: 575. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060575

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