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  • Title: Study with positron emission tomography of the osmotic opening of the dog blood-brain barrier for quinidine and morphine.
    Author: Agon P, Kaufman JM, Goethals P, Van Haver D, Bogaert MG.
    Journal: J Pharm Pharmacol; 1988 Aug; 40(8):539-43. PubMed ID: 2907006.
    Abstract:
    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.
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