2003 Fiscal Year Final Research Report Summary
脳シグマ受容体を指標にした加齢・神経変性疾患・脳腫瘍の新しいPET診断法
| Project/Area Number |
13557077
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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 | 展開研究 |
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| Research Field |
Radiation science
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| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
ISHIWATA Kiichi TOKYO METROPOLITAN FOUNDATION FOR RESEARCH ON AGING AND PROMOTION OF HUMAN WELFARE, TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, POSITRON MEDICAL RESEARCH GROUP, LEADER, 東京都老人総合研究所・ポジトロン医学研究グループ, 副参事研究員 (50143037)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Yuichi TOKYO METROPOLITAN FOUNDATION FOR RESEARCH ON AGING AND PROMOTION OF HUMAN WELFARE, TOKYO METROPOLITAN INSTITUTE QF GERONTOLOGY, POSITRON MEDICAL RESEARCH GROUP, SENIOR RESEARCH SCIENTIST, 福祉振興財団・東京都老人総合研究所・ポジトロン医学研究グループ, 主任研究員 (60205002)
NARIAI Tadashi TOKYO MEDICAL AND DENTAL UNIVERSITY, DEPARTMENT OF NEUROSUGERY, LECTURER, 大学院・医歯学総合研究科, 講師 (00228090)
ISHII Kenji TOKYO METROPOLITAN FOUNDATION FOR RESEARCH ON AGING AND PROMOTION OF HUMAN WELFARE, TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, POSITRON MEDICAL RESEARCH GROUP, RESEARCH SCIENTIST, 福祉振興財団・東京都老人総合研究所・ポジトロン医学研究グループ, 研究助手 (10231135)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Sigma receptor / Positron emission tomography / Alzheimer's disease / Parkinson's disease / Schizophrenia / Receptor occupancy / P-glycoprotein / Tumor diagnosis |
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| Research Abstract |
We developed [^<11>C]SA4503 as a radioligand for mapping sigma_1 receptors in the central nervous system by positron emission tomography (PET), and successfully visualized the sigma_1 receptors in the human brain at 2000 for the first time. The purposes of the present project are 1)establishment of quantitative measurement of the brain sigma_1 receptors by PET and [^<11>C]SA4503,2)application of the [^<11>C]SA4503 PET to diagnosis of neurological and psychiatric diseases,3)basic studies on the sigma_1 receptors and 4)development of new tracers including radioligands for sigma_2 receptor subtype.
We obtained the following findings.
1.In general densities of neuroreceptors decrease with aging. However, the binding of radiolabeled SA4503 increased in the rat and monkey brain. The human brain also showed a similar tendency.
2.In patients with Alzheimer's disease, the [^<11>C]SA4503 PET detected more sensitively degeneration of the brain than the [^<18>F]FDG PET.
3.In patients with Parkinson's disease, the binding of [^<11>C]SA4503 significantly decreased in the affected than the less affected side of the anterior putamen as observed in the [^<11>C]CFT binding.
4.Sigma_1 receptor occupancy by haloperidol was evaluated by [^<11>C]SA4503 PET, which would address pharmacological effects of neuroleptics in term of their sigma_1 receptor occupancy.
5.The [^<11>C]SA4503 PET may be useful for patients with schizophrenia.
6.The [^<11>C]SA4503 PET has potential for tumor diagnosis in the hypogastrium because of low accumulation levels of the activity.
7.Brain uptake of [^<11>C]SA4503 was not mediated by P-glycoprotein.
8.Several ^<11>C and ^<18>F analogs of [^<11>C]SA4503 were synthesized and evaluated in vivo. Among them we found [^<18>F]FE-SA4503 to be a promising radioligands for tumor diagnosis by PET.
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Research Products
(24 results)
