title: Kinetic study of benzyl [1-14C]acetate as a potential probe for astrocytic energy metabolism in the rat brain: Comparison with benzyl [2-14C]acetate.
abstract: Brain uptake of [(14)C]acetate has been reported to be a useful marker of astrocytic energy metabolism. In addition to uptake values, the rate of radiolabeled acetate washout from the brain appears to reflect CO2 exhaustion and oxygen consumption in astrocytes. We measured the time-radioactivity curves of benzyl [1-(14)C]acetate ([1-(14)C]BA), a lipophilic probe of [1-(14)C]acetate, and compared it with that of benzyl [2-(14)C]acetate ([2-(14)C]BA) in rat brains. The highest brain uptake was observed immediately after injecting either [1-(14)C]BA or [2-(14)C]BA, and both subsequently disappeared from the brain in a single-exponential manner. Estimated [1-(14)C]BA washout rates in the cerebral cortex and cerebellum were higher than those of [2-(14)C]BA. These results suggested that [1-(14)C]BA could be a useful probe for estimating the astrocytic oxidative metabolism. The [1-(14)C]BA washout rate in the cerebral cortex of immature rats was lower than that of mature rats. An autoradiographic study showed that the washout rates of [1-(14)C]BA from the rat brains of a lithium-pilocarpine-induced status epilepticus model were not significantly different from the values in control rat brains except for the medial septal nucleus. These results implied that the enhancement of amino acid turnover rate rather than astrocytic oxidative metabolism was increased in status epilepticus.
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan mokada@nirs.go.jp.
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanamoto
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kagawa
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Hosoi
authors.affiliation: Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Suita, Japan Department of Drug Metabolism & Pharmacokinetics, Research Laboratory for Development, Shionogi & Co., Ltd., Toyonaka, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001345:Autoradiography; D001593:Benzyl Compounds / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004734:Energy Metabolism; D008297:Male; D010084:Oxidation-Reduction; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001593:Benzyl Compounds; D019275:Radiopharmaceuticals; C046412:benzyl acetate
keywords: Astrocytic oxidative metabolism; benzyl [1-14C]acetate; benzyl [2-14C]acetate; kinetics; washout rate