title: Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia: a PET study in rat and canine models of focal cerebral ischemia.
abstract: Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. We speculate that [1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [15O]H2O measured 1-2 h and 5-6 h after insult was compared with that of [1-11C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [15O]H2O were lower than those determined with [1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1-11C]octanoate was observed in the ischemic regions. The uptake of [1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1-11C]octanoate provides functional information different from CBF. In conclusion, we found that [1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia.
authors.affiliation: Institute for Biofunctional Research Co., Ltd. Department of Tracer Kinetics, Hokkaido University School of Medicine, Sapporo, Japan. kuge@med.hokudai.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kuge
authors.forename: H
authors.initials: H
authors.lastname: Kawashima
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Imanishi
authors.forename: M
authors.initials: M
authors.lastname: Shiomi
authors.forename: K
authors.initials: K
authors.lastname: Minematsu
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: N
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002210:Caprylates / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004285:Dogs; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002210:Caprylates; D002250:Carbon Radioisotopes; C031492:octanoic acid