2005 Fiscal Year Final Research Report Summary
In-vivo quantification analysis of activated microglia in the brain of dementia
| Project/Area Number |
16591177
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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 |
Psychiatric science
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
SUZUKI Kazutoshi National Institute of Radiological Sciences, Researcher, 分子認識研究グループ, 研究員 (90162932)
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| Co-Investigator(Kenkyū-buntansha) |
SUHARA Tetsuya National Institute of Radiological Sciences, Special Researcher, 脳機能イメージング研究開発推進室, 研究員 (90216490)
IKEJIRI Yoshitaka Graduate School of Medicine Osaka University, Psychiatry and Behavioral Science, Assistant Professor, 医学部精神神経科, 講師 (30294086)
ASADA Takashi Institute of Clinical Medicine University of Tsukuba, Department of Neuropsychiatry, Professor, 医学部精神神経科, 教授 (90184142)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Alzheimer disease / dementia / mild cognitive impairment / PET / peripheral benzodiazepine receptor / microglia / senile plaque / [^<11>C]DAA1106 |
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| Research Abstract |
As a maker for the early diagnosis of the dementia with PET, we developed the new radioactive ligand [^<11>C]DAA1106, which has high permeability to the brain and shows high affinity and specificity to the peripheral benzodiazepine receptor (PBR). In vitro and ex-vivo study using the model mouse of Alzheimer disease, we found the high density of PBR was localized in the activated microglia at surroundings of senile plaque of model mouse. The change of PBR in the brain of Alzheimer disease should reflect the activity of microglia related to the effect of senile plaque specific to neuronal degeneration in this disease.
We examined whether we can diagnose the dementia in early stage by the quantification of the PBR with PET using [^<11>C]DAA1106 in in-vivo human study. We performed the PET scan with [^<11>C]DAA1106 on the group of patients of Alzheimer disease (n=10) and age-matched control group (n=11). Results showed significant increase of PBR-binding potential (BP) in the broad brain regions in the group of Alzheimer disease when compared to the age-matched control group. Further, to examine whether we can diagnose the dementia in very early stage before appearance of demented symptoms, we performed the scan on the subjects who had mild cognitive impairment (MCI), but cannot be diagnosed as the dementia at the time of PET scanning (n=7). We found the significant increase of PBR-BP in this group in broad brain regions when compared to the control group.
In conclusion, it was shown that PET scan with [^<11>C]DAA1106 can show the increase of PBR which might be related to the neurodegenerative process in the Alzheimer disease. In most of the cases, MCI can be regarded as the pre-stage of dementia, and we can detect the abnormality of PBR-BP even before symptoms of dementia clearly appeared. PET scan with [^<11>C]DAA1106 should be useful method for the early diagnosis of the dementia and other neuronal degenerative diseases.
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[Journal Article] [2-^<11>C]Isopropyl-, [1-^<11>C]Ethyl- and [^<11>C]Methyl- labeled phenoxyphenyl acetamide derivatives as PET ligands for peripheral benzodiazepine receptor : radiosynthesis, uptake and in vivo binding in brain.2006
Author(s)
Zhang M.-R., Ogawa M., Maeda J., Ito T., Noguchi J., Kumata K., Okauchi T., Suhara T., Suzuki K.
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Journal Title
J Med Chem 49
Pages: 2735-2742
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Quantitative Analyses of 18F-FEDAA1106 Binding to Peripheral Benzodiazepine Receptors in Living Human Brain.2006
Author(s)
Fujimura Y, Ikoma Y, Yasuno F, Suhara T, Ota M, Matsumoto R, Nozaki S, Takano A, Kosaka J, Zhang MR, Nakao R, Suzuki K, Kato N, Ito H.
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Journal Title
J Nucl Med 47
Pages: 43-50
Description
「研究成果報告書概要(和文)」より
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[Journal Article] [2-^<11>C]Isopropyl-, [1-^<11>C]Ethyl- and [^<11>C]Methyl- labeled phenoxyphenyl acetamide derivatives as 'PET ligands for peripheral benzodiazepine receptor: radiosynthesis, uptake and in vivo binding in brain.2006
Author(s)
Zhang M.-R., Ogawa M., Maeda J., Ito T., Noguchi J., Kumata K., Okauchi T., Suhara T., Suzuki K.
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Journal Title
J Med Chem 49
Pages: 2735-2742
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Development of a new radioligand, N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[^<18F>fluoroethyl-5-methoxy benzyl)acetamide, for PET imaging of peripheral benzodiazepine receptor in primate brain.2004
Author(s)
Zhang M.-R., Maeda J., Ogawa M., Noguchi J., Ito T., Yoshida Y., Okauchi T., Obayashi S., Suhara T., Suzuki K.
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Journal Title
J Med Chem 47
Pages: 2228-2235
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Development of a new radioligand, N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[^<18>F]fluoroethyl-5-methox ybenzyl)acetamide, for PET imaging of peripheral benzodiazepine receptor in primate brain.2004
Author(s)
Zhang M.-R., Maeda J., Ogawa M., Noguchi J., Ito T., Yoshida Y., Okauchi T., Obayashi S., Suhara T., Suzuki K.
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Journal Title
J Med Chem 47
Pages: 2228-2235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain.2004
Author(s)
Maeda J, Suhara T, Zhang MR, Okauchi T, Yasuno F, Ikoma Y, Inaji M, Nagai Y, Takano A, Obayashi S, Suzuki K.
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Journal Title
Synapse 52
Pages: 283-291
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [^<11>C]DAA1106.
Author(s)
Ikoma Y., Yasuno F., Ito H., Suhara T., Ota M., Toyama H., Fujimura Y., Takano A., Maeda J., Zhang M.-R., Nakao R., Suzuki K.
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Journal Title
J Cereb Blood Flow Metab (In Press)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [^<11>C]DAA1106.
Author(s)
Ikoma Y., Yasuno F., Ito H., Suhara T., Ota M., Toyama H., Fujimura Y., Takano A., Maeda J., Zhang M.-R., Nakao R., Suzuki K.
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Journal Title
J Cereb Blood Flow Metab (in press)
Description
「研究成果報告書概要(欧文)」より
