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Fully automated GMP production of [Ga-68]Ga-DO3A-VS-Cys(40)-Exendin-4 for clinical use
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
2017 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 3, p. 111-125Article in journal (Refereed) Published
Abstract [en]

[Ga-68]Ga-DO3A-VS-Cys(40)-Exendin-4/PET-CT targeting glucagon like peptide-1 receptor (GLP-1R) has previously demonstrated its potential clinical value for the detection of insulinomas. The production and accessibility of this radiopharmaceutical is one of the critical factors in realization of clinical trials and routine clinical examinations. Previously, the radiopharmaceutical was prepared manually, however larger scale of clinical trials and healthcare requires automation of the production process in order to limit the operator radiation dose as well as improve tracer manufacturing robustness and on-line documentation for enhanced good manufacturing practice (GMP) compliance. A method for Ga-68-labelling of DO3A-VS-Cys(40)-Exendin-4 on a commercially available synthesis platform was developed. Equipment such as Ge-68/Ga-68 generator, synthesis platform, and disposable cassettes for Ga-68-labelling used in the study was purchased from Eckert & Ziegler. DO3A-VS-Cys(40)-Exendin-4 was synthesized in-house. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, pH, product purification step were investigated and optimised. Reproducible and GMP compliant automated production of [Ga-68]Ga-DO3A-VS-Cys(40)-Exendin-4 was developed. Exendin-4 comprising methionine amino acid residue was prone to oxidation which was strongly influenced by the elevated temperature, radioactivity amount, and precursor concentration. The suppression of the oxidative radiolysis was achieved by addition of ethanol, dihydroxybenzoic acid and ascorbic acid to the reaction buffer as well as by optimizing heating temperature. The non-decay corrected radiochemical yield was 43 +/- 2% with radiochemical purity of over 90% wherein the individual impurity signals in HPLC chromatogram did not exceed 5%. Automated production and quality control methods were established for paving the pathway for broader clinical use of [Ga-68]Ga-DO3A-VS-Cys(40)-Exendin-4.

Place, publisher, year, edition, pages
2017. Vol. 7, no 3, p. 111-125
Keyword [en]
Exendin-4, Insulinoma, GLP-1, GMP, Gallium-68, automation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-335532ISI: 000409370800002PubMedID: 28721305OAI: oai:DiVA.org:uu-335532DiVA, id: diva2:1163987
Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-08Bibliographically approved

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