| Project/Area Number |
06672142
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SAJI Hideo Kyoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40115853)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | nicotine receptor / optical isomer / radiopharmaceutical / brain / radioiodine / nuclear medicine / biodistribution / radioreceptor assay / 放射性医薬品 / アルツハイマー病 / 老化 / 病態モデル動物 / 核医学診断 |
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| Research Abstract |
Changes in the density of nicotine receptors have recently been reported in the brains of patients with various disorders, including Alzheimer's disease. These obsevations have stimulated interest in means of imaging the distribution of brain nicotinic receptors noninvasively in vivo with nuclear medicinal imaging techniques such as SPECT.In this study, the superior radiation properties of 123-I for SPECT prompted us to synthesize a radioiodinated nicotine analog with high receptor affinity. Thus, (S) 5-iodonicotine (INC), an (S) -nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by SPECT.[125I] - (S) -INC was synthesized with high specific radioactivity. The binding data of INC for brain nicotine receptors revealed that the affinity of INC was the same as that of (S) -nicotine and 80-fold higher than the (R) -enantiomer. Biodistribution studies in mice disclosed that the brain uptake of INC was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125-I] -INC was correlated well with the distribution of nicotine receptors reported from in vitro studies. (R) -enantiomer showed more rapid washout the brain and smaller regional cerebral distribution than (S) -enantiomer. Thus, INC bound to brain nicotine receptors in vivo and therefore 123-I-INC may be a potential radioligand for use in in vivo cerebral nicotinic receptor studies by SPECT.
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