Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates
The development of <sup>64</sup>Cu-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 tra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/1/75 |
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| author | Aurélie Maisonial-Besset Tiffany Witkowski Mercedes Quintana Sophie Besse Vincent Gaumet Axel Cordonnier Cyrille Alliot Aurélien Vidal Caroline Denevault-Sabourin Sébastien Tarrit Sophie Levesque Elisabeth Miot-Noirault Jean-Michel Chezal |
| author_facet | Aurélie Maisonial-Besset Tiffany Witkowski Mercedes Quintana Sophie Besse Vincent Gaumet Axel Cordonnier Cyrille Alliot Aurélien Vidal Caroline Denevault-Sabourin Sébastien Tarrit Sophie Levesque Elisabeth Miot-Noirault Jean-Michel Chezal |
| author_sort | Aurélie Maisonial-Besset |
| collection | DOAJ |
| description | The development of <sup>64</sup>Cu-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 [<sup>64</sup>Cu]Cu-15-5 complex prompted us to investigate its potential for the <sup>64</sup>Cu-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 <sup>64</sup>Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [<sup>64</sup>Cu]Cu-15-5- and [<sup>64</sup>Cu]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. |
| first_indexed | 2024-03-09T09:44:51Z |
| format | Article |
| id | doaj.art-89ab06b2726f431d8c2c4fbde3d019d8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T09:44:51Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-89ab06b2726f431d8c2c4fbde3d019d82023-12-02T00:40:20ZengMDPI AGMolecules1420-30492022-12-012817510.3390/molecules28010075Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of ImmunoconjugatesAurélie Maisonial-Besset0Tiffany Witkowski1Mercedes Quintana2Sophie Besse3Vincent Gaumet4Axel Cordonnier5Cyrille Alliot6Aurélien Vidal7Caroline Denevault-Sabourin8Sébastien Tarrit9Sophie Levesque10Elisabeth Miot-Noirault11Jean-Michel Chezal12Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceGIP Arronax, F-44800 Saint-Herblain, FranceGIP Arronax, F-44800 Saint-Herblain, FranceGICC EA7501, Team IMT, Université de Tours, UFR de Médecine, Bâtiment Vialle, 10 Boulevard Tonnellé, BP 3223, CEDEX 01, 37032 Tours, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceDepartment of Nuclear Medicine, Jean Perrin Comprehensive Cancer Centre, F-63011 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceThe development of <sup>64</sup>Cu-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 [<sup>64</sup>Cu]Cu-15-5 complex prompted us to investigate its potential for the <sup>64</sup>Cu-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 <sup>64</sup>Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [<sup>64</sup>Cu]Cu-15-5- and [<sup>64</sup>Cu]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.https://www.mdpi.com/1420-3049/28/1/75copper-64chelating macrocyclesNODAGADOTA15-5trastuzumab |
| spellingShingle | Aurélie Maisonial-Besset Tiffany Witkowski Mercedes Quintana Sophie Besse Vincent Gaumet Axel Cordonnier Cyrille Alliot Aurélien Vidal Caroline Denevault-Sabourin Sébastien Tarrit Sophie Levesque Elisabeth Miot-Noirault Jean-Michel Chezal Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates Molecules copper-64 chelating macrocycles NODAGA DOTA 15-5 trastuzumab |
| title | Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates |
| title_full | Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates |
| title_fullStr | Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates |
| title_full_unstemmed | Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates |
| title_short | Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the <sup>64</sup>Cu-Labelling of Immunoconjugates |
| title_sort | synthesis and in vitro comparison of dota nodaga and 15 5 macrocycles as chelators for the sup 64 sup cu labelling of immunoconjugates |
| topic | copper-64 chelating macrocycles NODAGA DOTA 15-5 trastuzumab |
| url | https://www.mdpi.com/1420-3049/28/1/75 |
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