Two-Photon Fluorescence and Magnetic Resonance Specific Imaging of Aβ Amyloid Using Hybrid Nano-GdF 3 Contrast Media

Francis Mpambani (1) , Andreas K.O. Åslund (2, 3) , Frédéric Lerouge (1) , Sofie Nyström (3) , Nina Reitan (2) , Else Marie Huuse (2) , Marius Widerøe (2) , Frédéric Chaput (1) , Cyrille Monnereau (1) , Chantal Andraud (1) , Marc Lecouvey (4) , Susann Handrick (5) , Stefan Prokop (5) , Frank Heppner (5) , Peter Nilsson (3) , Per Hammarström (3) , Mikael Lindgren (2) , Stephane Parola (1)

1 LC - Laboratoire de Chimie - UMR5182
2 NTNU - Norwegian University of Science and Technology [Trondheim]
3 Linköpings universitet
4 CSPBAT - Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques
5 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]

Real time in vivo detection of Amyloid β (Aβ) deposits at an early stage may lead to faster and more conclusive diagnosis of Alzheimer’s disease (AD) and can facilitate the follow up of the effect of therapeutic interventions. In this work, the capability of new hybrid nanomaterials to target and detect Aβ aggregates using magnetic resonance (MRI) and fluorescence imaging is demonstrated. These smart contrast agents contain paramagnetic nanoparticles surrounded by luminescent conjugated oligothiophenes (LCOs) known to selectively bind to Aβ aggregates, with emission spectra strongly dependent on their conformations, opening the possibilities for several fluorescence imaging modes for AD diagnostics. Relaxivity is evaluated in vitro and ex vivo. The capability of these contrast media to link to Aβ fibrils in stained sections is revealed using transmission electron microscopy and fluorescence microscopy. Preliminary in vivo experiments show the ability of the contrast agent to diffuse through the blood–brain barrier of model animals and specifically stain amyloid deposits.

Domaines: Catalyse; Matériaux; Chimie organique; Chimie inorganique

Francis Mpambani, Andreas K.O. Åslund, Frédéric Lerouge, Sofie Nyström, Nina Reitan, et al.. Two-Photon Fluorescence and Magnetic Resonance Specific Imaging of Aβ Amyloid Using Hybrid Nano-GdF 3 Contrast Media. ACS Applied Bio Materials, 2018, 1 (2), pp.462 - 472. ⟨10.1021/acsabm.8b00191⟩. ⟨hal-01889053⟩