0000000000330288
AUTHOR
Robin Lescure
Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties
International audience; Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based o…
A Promising Family of Fluorescent Water-Soluble aza-BODIPY Dyes for in Vivo Molecular Imaging.
A new family of water-soluble and bioconjugatable aza-BODIPY fluorophores was designed and synthesized using a boron- functionalization strategy. These dissymmetric bis-ammonium aza-BODIPY dyes present optimal properties for a fluorescent probe; i.e., they are highly water-soluble, very stable in physiological medium; they do not aggregate in PBS, possess high quantum yield; and finally, they can be easily bioconjugated to antibodies. Preliminary in vitro and in vivo studies were performed for one of these fluorophores to image PD-L1 (Programmed Death-Ligand 1), highlighting the high potential of these new probes for future in vivo optical imaging studies.
Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore
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 [111In] 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 goo…
Development of functionalizable azaBODIPYs for the conception of theranostic agents and bimodal probes for imaging uses
The in vivo use of optical imaging is still limited by the lack of near infrared emitting probes. This thesis work focuses on the optimization and valorization of a water-soluble fluorescent platform whose optical properties enable an in vivo use. Two distinct applications were investigated for this WazaBY (Water-soluble azaBODIPY) platform: use as a PET (or SPECT) / optical bimodal probe, and as a theranostic agent. Concerning the first project, we were able to develop a targetted SPECT/optical bimodal probe, which was radiometallated with indium 111. Using xenografted murine models, we were able to show a clear accumulation of the probe in the tumor 24 hours after injection. Moreover, the…