Fiche publication
Date publication
novembre 2023
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck
,
Dr GONCALVES Victor
Tous les auteurs :
Vivier D, Hautière M, Pineau D, Dancer PA, Herbet A, Hugnot JP, Bernhard C, Goncalves V, Truillet C, Boquet D, Denat F
Lien Pubmed
Résumé
For the past two decades, the emerging role of the endothelin (ET) axis in cancer has been extensively investigated, and its involvement in several mechanisms described as "hallmarks of cancer" has clearly highlighted its potential as a therapeutic target. Despite the growing interest in finding effective anticancer drugs, no breakthrough treatment has successfully made its way to the market. Recently, our team reported the development of a new immuno-positron emission tomography probe targeting the ET A receptor (ET, one of the ET receptors) that allows the successful detection of ET glioblastoma, paving the way for the elaboration of novel antibody-based strategies. In this study, we describe the synthesis of two PET/NIRF (positron emission tomography/near-infrared fluorescence) dually functionalized imaging agents, directed against ET or ET, that could be used to detect ET tumors and select patients that will be eligible for fluorescence-guided surgery. Both imaging modalities were brought together using a highly versatile tetrazine platform bearing the IRDye800CW fluorophore and desferrioxamine for Zr chelation. This so-called monomolecular multimodal imaging probe was then "clicked", via an inverse-electron-demand Diels-Alder reaction, to antibodies conjugated site-specifically with a -cyclooctene group. This approach has led to homogeneous and well-defined constructs that retained their high affinity and high specificity for their respective target, as shown by flow cytometry and NIRF in vivo imaging experiments in nude mice bearing CHO-ET and CHO-ET tumors. Ultimately, these bimodal immunoconjugates could be used to improve the outcomes of patients with ET tumors.
Référence
Bioconjug Chem. 2023 11 6;:
