Fiche publication
Date publication
octobre 2025
Journal
Molecular pharmaceutics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck
,
Dr GONCALVES Victor
Tous les auteurs :
Vizier R, Boswinkel M, Moreau M, Faivre J, Carrierre M, Cheveau M, Poty S, Denat F, van Lith SAM, Goncalves V
Lien Pubmed
Résumé
Monoclonal antibodies have proven to be highly effective for in vivo targeting in nuclear medicine applications. However, typical radiolabeling methods, for PET/SPECT imaging and targeted radionuclide therapy, often require conditions that may affect the structural integrity of these fragile biomolecules. In this study, we introduce a novel methodology, based on supramolecular chemistry, for efficient radiolabeling of antibodies under mild conditions. Specifically, we report the synthesis of DOTA-cucurbit[7]uril (DOTA-CB[7]), a precursor that can be readily radiolabeled with a variety of radionuclides (In, Ga, Zr, Lu, Ac). [In]In-DOTA-CB[7] was conjugated to an anti-HER2 antibody (trastuzumab) site─specifically grafted with adamantan-1-amine groups. The supramolecular conjugation, driven by the exceptionally strong affinity between CB[7] and adamantan-1-amine enabled rapid and efficient formation of a stable antibody-radiometal complex under mild conditions. The resulting radioimmunoconjugate demonstrated high in vitro and in vivo stability and effective targeting of HER2+ tumors, as evidenced by SPECT/CT imaging in mice xenografted with HER2+ SKOV-3 cells. These findings highlight the potential of DOTA-CB[7] for supramolecular radiolabeling, offering a simple and versatile alternative to traditional covalent approaches, particularly for applications requiring compatibility with heat-sensitive biomolecules.
Mots clés
SPECT/CT, antibodies, bioconjugation, cucurbituril, supramolecular chemistry
Référence
Mol Pharm. 2025 10 13;:
