2004 Fiscal Year Final Research Report Summary
NORMAL DISTRIBUTION OF NICOTINIC ACETYLCHOLINE RECEPTORS IN NON-SMOKERS AND SMOKERS : 5IA-SPELT STUDY.
| Project/Area Number |
15591268
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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 |
ISHIZU Koichi KYOTO UNIVERSITY, MEDICINE, Assistant Professor, 医学研究科, 助手 (50314224)
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| Co-Investigator(Kenkyū-buntansha) |
IIDA Yasuhiko GUNMA UNIVERSITY, MEDICINE, Associate Professor, 医学部, 助教授 (60252425)
MUKAI Takahiro KYUSYU UNIVERSITY, PHARMACOLOGY, Associate Professor, 薬学研究院, 助教授 (30284706)
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| Project Period (FY) |
2003 – 2004
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| Keywords | 5IA / nicotine / SPECT / nAChR / quantitative / smoking / acetylcholine receptor |
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| Research Abstract |
We have demonstrated suitability of 123I-(S)-5-iodo-3-(2-azetidinylmethoxy) pyridine, 123I-5-iodo-A-85380(123I-5IA) to image in vivo nicotinic acetylcholine receptors in human brain. This distribution of 123I-5IA in normal volunteer was compatible with the known distribution of nicotinic receptors in humans. The present study was designed to demonstrate the in vivo temporal changes of high affinity nicotinic acetylcholine receptors (nAChR) in smokers before and after cigarette withdrawal using 123I-5IA. Subjects were four smokers free of any neurological diseases (1 female and 3 males, 26 to 30 yrs, mean 28.3+/-2.1). They underwent two dynamic SPECT (Picker, Prism 3000) studies, 4 hours after and 20 days after cigarette smoking withdrawal. All of them received a one-minute intravenous injection of approximately 150 MBq of 123I-5IA in both studies. Arterial input function was obtained for each subject and a two-compartment model was used to determine the kinetic parameters of 123I-5IA u
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sing data from 6 hours SPECT scan. The distribution volume (Vt)(ml/ml) of 123I-5IA, which is related to the number of unoccupied binding sites in the brain, was calculated and compared to previous results generated from normal non-smoker volunteers. The 123I-5IA Vt (ml/ml) values in the smokers are shown in Table 1. The highest Vt values were observed in thalamus and brain stem at both steps of the study. The Vt values were significantly higher after cigarette smoking withdrawal (p<0.01) as compared to the smoking study with 4 hours smoking withdrawal The Vt values from smokers were significant lower as compared to the values from normal non-smokers (p<0.05). No significant difference was observed between Vt values after cigarette smoking withdrawal. and those of the non-smokers. In conclusion, 123I-5IA-SPECT was valuable in assessing quantitative temporal changes of nAChR distribution in smoker's brain as measured before and after cigarette withdrawal. Up-regulation of nAChR was observed after 20 days cigarette withdrawal in the smokers. Less
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