التفاصيل البيبلوغرافية
| العنوان: |
Automated GMP-Compliant Production of [68Ga]Ga-DO3A-Tuna-2 for PET Microdosing Studies of the Glucagon Receptor in Humans. |
| المؤلفون: |
Wagner, Michael, Doverfjord, Johan G., Tillner, Joachim, Antoni, Gunnar, Haack, Torsten, Bossart, Martin, Laitinen, Iina, Johansson, Lars, Pierrou, Stefan, Eriksson, Olof, Velikyan, Irina |
| المصدر: |
Pharmaceuticals (14248247); Aug2020, Vol. 13 Issue 8, p176-176, 1p |
| مصطلحات موضوعية: |
GLUCAGON receptors, MANUFACTURING processes, RADIOCHEMICAL purification, CURRENT good manufacturing practices, ENDOTOXINS, GLUCAGON-like peptide-1 agonists, PROCESS optimization |
| مصطلحات جغرافية: |
GERMANY |
| مستخلص: |
Introduction: [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 (previously published as [68Ga]Ga-DO3A-VS-Cys40-S01-GCG) has shown high-affinity specific binding to the glucagon receptor (GCGR) in vitro and in vivo in rats and non-human primates in our previous studies, confirming the suitability of the tracer for drug development applications in humans. The manufacturing process of [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 was automated for clinical use to meet the radiation safety and good manufacturing practice (GMP) requirements. Methods: The automated synthesis platform (Modular-Lab PharmTrace, Eckert & Ziegler, Eurotope, Germany), disposable cassettes for 68Ga-labeling, and pharmaceutical-grade 68Ge/68Ga generator (GalliaPharm®) used in the study were purchased from Eckert & Ziegler. The parameters such as time, temperature, precursor concentration, radical scavenger, buffer concentration, and pH, as well as product purification step, were investigated and optimized. Process optimization was conducted with regard to product quality and quantity, as well as process reproducibility. The active pharmaceutical ingredient starting material DO3A-VS-Cys40-Tuna-2 (GMP-grade) was provided by Sanofi Aventis. Results: The reproducible and GMP-compliant automated production of [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 with on-line documentation was developed. The non-decay-corrected radiochemical yield was 45.2 ± 2.5% (n = 3, process validation) at the end of the synthesis with a labeling synthesis duration of 38 min and a quality controlincluding release procedure of 20 min. The radiochemical purity of the product was 98.9 ± 0.6% (n = 17) with the total amount of the peptide in the preparation of 48 ± 2 µg (n = 3, process validation). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity tests met the acceptance criteria. The product was stable at ambient temperature for at least 2 h. Conclusion: The fully automated GMP-compliant manufacturing process was developed and thoroughly validated. The resulting [68Ga]Ga-DO3A-VS-Cys40-Tuna-2 was used in a clinical study for accurate quantification of GCGR occupancy by a dual anti-diabetic drug in vivo in humans. [ABSTRACT FROM AUTHOR] |
|
Copyright of Pharmaceuticals (14248247) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder