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Monitoring In Vivo Performances of Protein–Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging

Abstract : In preclinical models, the development and optimization of protein−drug conjugates require accurate determination of the plasma and tissue profiles of both the protein and its conjugated drug. To this aim, we developed a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging. By combining enzymatic and chemical reactions, we obtained homogeneous dual-labeled anti-MMP-14 Fabs (antigen-binding fragments) conjugated to monomethyl auristatin E where the protein scaffold was labeled with carbon-14 (14C) and the conjugated drug with tritium (3H). These antibody−drug conjugates with either a noncleavable or a cleavable linker were then evaluated in vivo. By combining liquid scintillation counting and ex vivo dual-isotope radio-imaging, it was possible not only to monitor both components simultaneously during their circulation phase but also to quantify accurately their amount accumulated within the different organs.
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https://hal-cea.archives-ouvertes.fr/cea-03834302
Contributor : Mathilde Keck Connect in order to contact the contributor
Submitted on : Friday, November 4, 2022 - 10:39:04 AM
Last modification on : Wednesday, November 9, 2022 - 4:44:16 PM

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Héloïse Cahuzac, Antoine Sallustrau, Carole Malgorn, Fabrice Beau, Peggy Barbe, et al.. Monitoring In Vivo Performances of Protein–Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging. Journal of Medicinal Chemistry, 2022, 65 (9), pp.6953 - 6968. ⟨10.1021/acs.jmedchem.2c00401⟩. ⟨cea-03834302⟩

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