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Radiopharmaceutical Formulation and Preclinical Testing of 68Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial.
Hörmann, Anton A; Klingler, Maximilian; Rangger, Christine; Mair, Christian; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene J; von Guggenberg, Elisabeth.
Afiliación
  • Hörmann AA; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Klingler M; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Rangger C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Mair C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Decristoforo C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Uprimny C; Department of Nuclear Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Virgolini IJ; 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.
Pharmaceuticals (Basel) ; 14(6)2021 Jun 16.
Article en En | MEDLINE | ID: mdl-34208516
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceuticals (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Suiza