Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore.
Fiche publication
Date publication
août 2021
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BETTAIEB Ali, Pr PAUL Catherine, Pr DENAT Franck, Dr COLLIN Bertrand, Dr BELLAYE Pierre-Simon
Tous les auteurs :
Privat M, Bellaye PS, Lescure R, Massot A, Baffroy O, Moreau M, Racoeur C, Marcion G, Denat F, Bettaieb A, Collin B, Bodio E, Paul C, Goze C
Lien Pubmed
Résumé
A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [In] indium and studied . The developed monomolecular multimodal imaging probe (MOMIP) is water-soluble and chemically and photochemically stable, emits in the near infrared (NIR) region (734 nm in aqueous media), and displays a good quantum yield of fluorescence (around 15%). Single-photon emission-computed tomography and fluorescence imaging have been performed in nude mice bearing HER2-overexpressing HCC1954 human breast cancer xenografts and have evidenced the good tumor targeting of the [In] In bimodal agent. Finally, the proof of concept of using it as a new tool for fluorescence-guided surgery has been shown.
Référence
J Med Chem. 2021 Aug 2;: