| Project/Area Number |
10670847
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
MAGATA Yasuhiro Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (20209399)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIZAWA Sadahiko Fukui Medical University, Biomedical Imaging Research Center, Associate Professor, 高エネルギー医学研究センター, 助教授 (70243011)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | glucose / metabolism / SPECT / hexokinase / I-125 / glucosamine |
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| Research Abstract |
In order to maintain homeostasis in the living organ, glucose metabolism is an essential biochemical reaction to produce energy, ATP. Nuclear medicine diagnosis is useful to determine the physiological and biochemical changes in diseased organs using some reaction rate parameters of glucose metabolism as indices. Evaluation of glucose metabolism parameters is an important point for nuclear medicine diagnosis. On these basis, a new radioiodinated glucose derivative was designed, synthesized and evaluated in vitro and in vivo.
N-(p-iodophenethyl)-glucosamine (IBGA) was synthesized and it was observed this compound inhibits competitively hexokinase reaction in vitro. Then it was radiolabeled with I-125 by iodine-iodine exchange reaction to evaluate in vivo characteristics. In vivo biodistribution study in mice showed a high uptake of the radioactivity in the heart in spite of low uptake in the brain. Although this mechanism of high uptake in the heart is still unclear, it was indicated that heart images related to glucose metabolism can be obtained interestingly. On the other hand ,it was shown that the second position of the glucose is proper position for introduction of some groups to inhibit hexokinase reaction. To evaluate the effect of the introduced group size on the inhibition reactivity, 2-thioglucose (2-TG) was synthesized as a model compound. Thiol group is easily alkylated in alkaline condition. As a preliminary evaluation, C-11-methylated 2-TG was synthesize and studied in vivo biodistribution. Although the heart uptake was lower than of glucose, an accumulating type time activity curve was obtained. This result indicates probability of clinical usefulness of the artificial glucose analogues designed by this research.
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