التفاصيل البيبلوغرافية
| العنوان: |
Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64 Cu-Labelling of Immunoconjugates. |
| المؤلفون: |
Maisonial-Besset, Aurélie, Witkowski, Tiffany, Quintana, Mercedes, Besse, Sophie, Gaumet, Vincent, Cordonnier, Axel, Alliot, Cyrille, Vidal, Aurélien, Denevault-Sabourin, Caroline, Tarrit, Sébastien, Levesque, Sophie, Miot-Noirault, Elisabeth, Chezal, Jean-Michel |
| المصدر: |
Molecules; Jan2023, Vol. 28 Issue 1, p75, 20p |
| مصطلحات موضوعية: |
ANTIBODY-toxin conjugates, RADIOACTIVE tracers, MONOCLONAL antibodies, IMMUNE recognition, ETHYLENEDIAMINETETRAACETIC acid, TRASTUZUMAB, CANCER cells, RING formation (Chemistry) |
| مستخلص: |
The development of 64Cu-based immuno-PET radiotracers requires the use of copper-specific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [64Cu]Cu-15-5 complex prompted us to investigate its potential for the 64Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA- and 15-5-mAb conjugates were radiolabelled with 64Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [64Cu]Cu-15-5- and [64Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88–94%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition. [ABSTRACT FROM AUTHOR] |
|
Copyright of Molecules 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