Analysis of blood-brain barrier permeability for Nanobodies using microdialysis.

Guy Caljon, Vicky Caveliers, T. Lahoutte, P. De Baetselier, Jan Van Den Abbeele, Ilse Julia Smolders, Yvette Michotte, S. Muyldermans, Stefan Magez, Ralph Clinckers

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)

Abstract

Nanobodies are considered as very promising antigen-binding moieties for molecular imaging and therapeutic purposes due to their favorable pharmacological and pharmacokinetic properties. However, the possibility for monovalent Nanobodies to reach targets in the central nervous system (CNS) remains to be demonstrated.
We have assessed the blood-brain barrier permeability for Nb_An33, a Nanobody against the Trypanosoma brucei Variant-specific Surface Glycoprotein (VSG), in healthy rats and rats that are in the encephalitic stage of African trypanosomiasis and suffer from acute brain inflammation using intracerebral microdialysis, SPECT (Single Photon Emission Computed Tomography) or a combination of both methodologies. This enabled the quantification of unlabeled and (99m)Tc-labeled Nanobodies using respectively a sensitive VSG-based Nb-detection ELISA, radioactivity measurement in collected microdialysates and SPECT image analysis.
The combined read-out methodologies demonstrate that, while brain disposition of Nb_An33 upon intravenous injection is at the limit of detection in healthy rats, inflammation-induced damage to the blood-brain barrier significantly increases (approximately 20 times) the Nanobody perfusion efficiency. Collectively, we illustrate the advantage of complementing SPECT analyses with intracerebral microdialysis in brain disposition studies and suggest that it is of interest to evaluate the blood-brain barrier penetrating potential of monovalent Nanobodies in models of CNS-inflammation. However, the pharmacokinetic properties that are considered favorable for peripheral imaging and therapeutic approaches might be key factors that preclude efficient application of Nanobodies to target the CNS.
Original languageEnglish
Title of host publicationUnknown
Publication statusPublished - 2010

Keywords

  • nanobodies
  • brain
  • microdialysis
  • blood-brain barrier

Fingerprint Dive into the research topics of 'Analysis of blood-brain barrier permeability for Nanobodies using microdialysis.'. Together they form a unique fingerprint.

Cite this