2006 Fiscal Year Final Research Report Summary
Development of RI probe for the measurement of glial metabolism.
| Project/Area Number |
16390339
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Osaka University |
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Principal Investigator |
INOUE Osamu Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50159969)
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| Co-Investigator(Kenkyū-buntansha) |
HATAZAWA Jun Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (70198745)
HOSOI Rie Osaka University, Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (30291446)
YAMAGUCHI Masatoshi Fukuoka University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (50117280)
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| Project Period (FY) |
2004 – 2006
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| Keywords | ^<14>C-acetate / Cerebral ischemia / Excitatory amino acid / Glial cell / Monocarboxylate transporter / Rat |
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| Research Abstract |
Evaluation of [^<14>C]-acetate as a selective RI probe for the measurement of glial metabolism in rodent brain was performed. A significant and dose-dependent decrease in [^<14>C]-acetate uptake in the striatum infused with fluorocitrate, a selective glial toxin, was seen, which indicated that [^<14>C]-acetate might reflect glial TCA cycle. Microinjection of ibotenic acid into rat striatum caused a significant enhancement of glucose utilization, whereas a significant reduction of [^<14>C]-acetate uptake and these changes in energy metabolism induced by excitatory amino acid were completely blocked by pretreatment with MK-801. [^<14>C]-Acetate uptake was sensitive against to a very short-term occlusion of middle cerebral artery (3-10 minutes) and reperfusion, more than 50% of reduction of [^<14>C]-acetate uptake in ischemic core was observed. In contrast, significant increases in [^<14>C]-acetate uptake in the brain of rats in other animal models such as Mn toxicity or Li-pilocarpine ep
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ilepsy were observed. These results indicated that [^<14>C]-acetate seemed to be a useful tool for the measurement of dysfunction of glial metabolism.
In order to improve the brain uptake, a new type of pro-radiotracer, which easily pass through the blood-brain-barrier, and rapidly converted to labeled acetate in the brain by carboxyl esterase. These kinds of [^<14>C]-phenylacetate and [^<14>C]-benzylacetate were synthesized, and evaluated their potential as a RI probe. Among them, [^<14>C]-benzylacetate showed the highest brain uptake (about two times higher than [^<14>C]-deoxyglucose). It was rapidly hydrolyzed in intact rat brain, and less than 5% of total radioactivity was remained as [^<14>C]-benzylacetate itself at 1 minute post injection of the tracer. Radiochemical analysis using TLC revealed that about 90% of [^<14>C]-benzylacetate was converted to [^<14>C]-glutamate and [^<14>C]-glutamine within 10 minutes after the tracer injection. These results strongly indicated that [^<14>C] ([^<11>C])-labeled benzylacetate seemed to have a high potential radio tracer for the measurement of glial metabolism in intact brain. Less
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Research Products
(25 results)
