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


METHODS
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.


CONCLUSIONS
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.
Kinderklinik der Universität Göttingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany. huelper@med.uni-goettingen.de
Petra
P
Hülper
Christian
C
Dullin
Wilfried
W
Kugler
Max
M
Lakomek
Bernhard
B
Erdlenbruch
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D019793:Fluorescein / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D005719:gamma-Globulins / Q000378:metabolism*
D005456:Fluorescent Dyes; D005719:gamma-Globulins; D005990:Glycerol; D019793:Fluorescein