2010 Fiscal Year Final Research Report
Development of pre-synaptic cholinergic nervous system imaging agent for Alzheimer's disease early diagnosis
| Project/Area Number |
19390316
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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 | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHIBA Kazuhiro Kanazawa University, 学際科学実験センター, 教授 (40143929)
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| Project Period (FY) |
2007 – 2010
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| Keywords | アセチルコリントランスポーター / 分子イメージング / SPECT / PET |
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| Research Abstract |
We have tried to develop a molecular imaging agent of acethylcholine transporter (VAChT) for Alzheimer's disease early diagnosis, because biochemical changes of the presynaptic cholinergic system have been related to the pathogenesis of Alzheimer's disease. We synthesized (-)-[^<11>C]-methylvesamicol((-)-[^<11>C]OMV) and radioiodinated trans-decalin-o-iodovesamicol(DOIV) as new acetylcholine transporter imaging agents. (-)-[^<11>C]OMV binding in the ipsilateral cortex to the lesion was significantly reduced by 22.0±6.7% compared with that in the contralateral region in kinetics study using disability model monkeys produced by selectively destroying the p75NTR-positive cells in the right hemisphere of the brain. DOIV exhibited in vitro a highest affinity for VAChT among our vesamicol analogs synthesized previously. These results suggested that (-)-[^<11>C]OMV may be useful in the study of dementia characterized by degeneration of the cholinergic neurotransmitter system. Furthermore, radioiodinated DOIV may be superior to (-)-[^<11>C]OMV as VAChT imaging agent.
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[Journal Article] The potential of (-)-o-[11C] methyl vesamicol for diagnosing cholinergic deficit dementia.2009
Author(s)
Shiba, K., Nishiyama, S., Tsukada, H., Ishiwata, K., Kawamura, K., Ogawa, K., Mori, H.
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Journal Title
Synapse Vol.63
Pages: 167-171
Peer Reviewed
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[Journal Article] A Change of in Vivo Characteristics Depending on Specific Activity of Radioiodinated (+)-2-[4-(4-iodophenyl) piperidino] cyclohexanol [(+)-pIV] as a Ligand for Sigma Receptor Imaging.2008
Author(s)
Akhter, N., Shiba, K.Ogawa, K., Tsuji, S., Kinuya, S., Nakajima, K, Mori, H.
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Journal Title
Nucl.Med.Biol. Vol.35
Pages: 29-34
Peer Reviewed
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[Journal Article] Rapid Reduction of al-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In vivo Treatment with Doxorubicine.2007
Author(s)
Waarde, AV., Shiba, K., de Jong, JR., Tshiwata, K., Dierckx, RA, Elsinga, PH.
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Journal Title
JNucl.Med. Vol.48
Pages: 1320-1326
Peer Reviewed
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[Journal Article] Synthesis and evaluation of fluorine -18- labeled SA4503 as a selective sigmal receptor ligand for positron emission tomography.2007
Author(s)
Kawamura, K., Tsukada, H., Shiba, K., Tsuji, C., Harada, N., Kimura, Y, Ishiwata, K.
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Journal Title
Nucl.Med.Biol. Vol.34
Pages: 571-577
Peer Reviewed
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