Study with positron emission tomography of the osmotic opening of the dog blood-brain barrier for quinidine and morphine.
A canine model was used to evaluate the possibilities offered by positron emission tomography (PET) for the study of drug distribution in the brain during altered states of the blood-brain barrier (BBB). PET was used to monitor the changes in the distribution of [11C]quinidine and [11C]morphine resulting from BBB-disruption by intracarotid infusion of a hyperosmolar mannitol solution. Injection of Evans blue dye allowing post-mortem evaluation of the degree of BBB-opening was used as a reference method. Brain radioactivity concentrations observed after i.v. injection of either [11C] quinidine or [11C]morphine were markedly increased by intracarotid mannitol infusion, whereas they were not affected by saline infusion. For both drugs a close correlation was found between the radioactivity concentrations and the degree of Evans blue staining within the brain hemispheres and within smaller regions of interest corresponding to quadrants of a hemisphere. This parallelism between the findings for radioactivity concentrations and Evans blue staining suggests that PET allows the detection of in-vivo changes in brain distribution of drugs resulting from alterations of the BBB permeability.
Agon
P
P
Heymans Institute of Pharmacology, University of Gent, Belgium.
Kaufman
J M
JM
Goethals
P
P
Van Haver
D
D
Bogaert
M G
MG
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004285:Dogs; D005070:Evans Blue; D008353:Mannitol / Q000494:pharmacology; D009020:Morphine / Q000378:metabolism*; D009995:Osmosis; D011802:Quinidine / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D008353:Mannitol; D005070:Evans Blue; D009020:Morphine; D011802:Quinidine