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

J Control Release. 2016 Dec 10:243:1-10. doi: 10.1016/j.jconrel.2016.09.019. Epub 2016 Oct 6.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Alzheimer Disease / metabolism
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Camelids, New World / immunology*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy / methods
  • Neurofibrillary Tangles / immunology*
  • Plaque, Amyloid / immunology*
  • Single-Domain Antibodies / immunology*
  • Single-Domain Antibodies / metabolism
  • Tissue Distribution

Substances

  • Single-Domain Antibodies