title: Drug distribution in dog brain studied by positron emission tomography.
abstract: We used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C-labelled antipyrine, imipramine, and quinidine. Twenty-five sequential scans of a transaxial slice of the head were performed within 90 min; radioactivity in plasma was measured in a gamma-counter. Following i.v. injection of [11C]antipyrine (50 mg kg-1; 9-68 mCi; n = 10), the decay of plasma activity was accompanied by rapid uptake in brain and variable uptake in muscle, immediately followed by a redistribution leading to equalization of the radioactivity in the tissues. Administration of [11C]imipramine (4 mg kg-1; 30-110 mCi; n = 8) was followed by a rapid build-up of a sustained gradient between high brain, and low plasma and muscle radioactivity. After i.v. injection of [11C]quinidine (1 mg kg-1; 11-87 mCi; n = 10), radioactivity in brain was low, with higher activity in plasma and muscle throughout the experiment. Positron emission tomography thus revealed for each drug a distinct pattern of distribution consistent with established properties of the compounds. This technique seems promising for the study of early drug distribution, notwithstanding certain limitations.
authors.affiliation: Heymans Institute of Pharmacology, University of Gent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Agon
authors.forename: R
authors.initials: R
authors.lastname: Braeckman
authors.forename: D
authors.initials: D
authors.lastname: Van Haver
authors.forename: H
authors.initials: H
authors.lastname: Denutte
authors.forename: P
authors.initials: P
authors.lastname: Goethals
authors.forename: H
authors.initials: H
authors.lastname: Donche
authors.forename: F
authors.initials: F
authors.lastname: Vermeullen
authors.forename: J
authors.initials: J
authors.lastname: Deman
authors.forename: J M
authors.initials: JM
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D004285:Dogs; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics*; D009132:Muscles / Q000000981:diagnostic imaging / Q000378:metabolism; D011802:Quinidine / Q000097:blood / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D011802:Quinidine; D007099:Imipramine; D000983:Antipyrine