Monitoring proteins using in vivo near-infrared time-domain optical imaging after 2-O-hexyldiglycerol-mediated transfer to the brain

Mol Imaging Biol. 2011 Apr;13(2):275-83. doi: 10.1007/s11307-010-0348-3.

Abstract

Purpose: The aim of the present study was to gain insight into the penetration, biodistribution, and fate of globulins in the brain after 2-O-hexyldiglycerol-induced blood-brain barrier opening.

Procedures: The spatial distribution of fluorescence probes was investigated after blood-brain barrier opening with intracarotid 2-O-hexyldiglycerol injection. Fluorescence intensity was visualized by microscopy (mice and rats) and by in vivo time-domain optical imaging.

Results: There was an increased 2-O-hexyldiglycerol-mediated transfer of fluorescence-labeled globulins into the ipsilateral hemisphere. Sequential in vivo measurements revealed that the increase in protein concentration lasted at least 96 h after administration. Ex vivo detection of tissue fluorescence confirmed the results obtained in vivo.

Conclusion: Globulins enter the healthy brain in conjunction with 2-O-hexyldiglycerol. Sequential in vivo near-infrared fluorescence measurements enable the visualization of the spatial distribution of antibodies in the brain of living small animals.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism*
  • Fluorescein / metabolism
  • Fluorescent Dyes / metabolism
  • Glycerol / analogs & derivatives*
  • Glycerol / pharmacology*
  • Imaging, Three-Dimensional / methods*
  • Mice
  • Molecular Weight
  • Rats
  • Rats, Wistar
  • Spectroscopy, Near-Infrared / methods*
  • Time Factors
  • Tissue Distribution / drug effects
  • gamma-Globulins / metabolism*

Substances

  • Fluorescent Dyes
  • gamma-Globulins
  • Glycerol
  • Fluorescein