Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets

Tengfei Li (1, 2) , Matthias Vandesquille (3, 4, 5) , Fani Koukouli (6) , Clémence Dudeffant (1, 3, 5) , Ihsen Youssef (1) , Pascal Lenormand (2) , Christelle Ganneau (4) , Uwe Maskos (6) , Christian Czech (7) , Fiona Grueninger (7) , Charles Duyckaerts (1) , Marc Dhenain (3, 5) , Sylvie Bay (4) , Benoît Delatour (1) , Pierre Lafaye (2)

1 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
2 Ingénierie des Anticorps (plate-forme) - Antibody Engineering (Platform)
3 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
4 Chimie des biomolécules
5 I2BM - Institut d'Imagerie BioMédicale
6 NISC - Neurobiologie intégrative des Systèmes cholinergiques
7 F. Hoffmann-La Roche AG, Pharmaceutical Research and Early Development, NORD DTA,

Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer’s disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles. Our results demonstrate that VHHs can be used as specific BBB-permeable probes for both extracellular and intracellular brain targets and suggest new avenues for therapeutic and diagnostic applications in neurology.

Keywords: VHH; Blood-brain barrier; In vivo imaging; Alzheimer's disease; Tau; Abeta

Domains: Neuroscience; Imaging; Geriatry and gerontology

Tengfei Li, Matthias Vandesquille, Fani Koukouli, Clémence Dudeffant, Ihsen Youssef, et al.. Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets. Journal of Controlled Release, 2016, 243, pp.1 - 10. ⟨10.1016/j.jconrel.2016.09.019⟩. ⟨pasteur-01375692⟩