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

Author:

Okada Maki1,Yanamoto Kazuhiko2,Kagawa Tomohiko2,Yoshino Keiko2,Hosoi Rie2,Abe Kohji34,Zhang Ming-Rong1,Inoue Osamu2

Affiliation:

1. Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

2. Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan

3. Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Suita, Japan

4. Department of Drug Metabolism & Pharmacokinetics, Research Laboratory for Development, Shionogi & Co., Ltd., Toyonaka, Japan

Abstract

Brain uptake of [14C]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 [1-14C]acetate ([1-14C]BA), a lipophilic probe of [1-14C]acetate, and compared it with that of benzyl [2-14C]acetate ([2-14C]BA) in rat brains. The highest brain uptake was observed immediately after injecting either [1-14C]BA or [2-14C]BA, and both subsequently disappeared from the brain in a single-exponential manner. Estimated [1-14C]BA washout rates in the cerebral cortex and cerebellum were higher than those of [2-14C]BA. These results suggested that [1-14C]BA could be a useful probe for estimating the astrocytic oxidative metabolism. The [1-14C]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 [1-14C]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.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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