Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore.
[en] 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 [(111)In] indium and studied in vivo. 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 [(111)In] In bimodal agent. Finally, the proof of concept of using it as a new tool for fluorescence-guided surgery has been shown.
Disciplines :
Chemistry
Author, co-author :
Privat, Malorie; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, ; Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research
Bellaye, Pierre-Simon; Service de médecine nucléaire, Centre Georges François Leclerc, 1 rue Professeur
Lescure, Robin; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302,
Massot, Aurélie; Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research
Baffroy, Océane; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302,
Moreau, Mathieu; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, ; Service de médecine nucléaire, Centre Georges François Leclerc, 1 rue Professeur
Racoeur, Cindy; Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research
Marcion, Guillaume ; Université de Liège - ULiège > Integrative Biological Sciences (InBioS) ; UMR INSERM/uB/AGROSUP 1231, Team 3 HSP-Pathies, labellisée Ligue Nationale contre
Denat, Franck; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302,
Bettaieb, Ali; Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research
Collin, Bertrand; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302, ; Service de médecine nucléaire, Centre Georges François Leclerc, 1 rue Professeur
Bodio, Ewen ; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302
Paul, Catherine; Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research
Goze, Christine ; Institut de Chimie Moléculaire de l'Université de Bourgogne, ICMUB UMR CNRS 6302
Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore.
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