1999 Fiscal Year Final Research Report Summary
In vivo PET measurement of expression of dopamine D2 receptor gene injected into rat striatum
| Project/Area Number |
10558115
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY |
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Principal Investigator |
ISHIWATA Kiichi Tokyo Metro. Inst. Gerontol., PET Center, Senior Res. Scientist, ポジトロン医学研究部門, 主任研究員 (50143037)
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| Co-Investigator(Kenkyū-buntansha) |
UMEGAKI Hiroyuki Nagoya Univ. School of Medicine, Associate Researcher, 医学部, 医員
SENDA Michio Tokyo Metro. Inst. Gerontol., PET Center, Chief of Department, ポジトロン医学研究部門, 研究室長 (00216558)
IGUCHI Akihisa Nagoya University School of Medicine, Professor, 医学部, 教授 (20109763)
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| Project Period (FY) |
1998 – 1999
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| Keywords | dopamine D2 receptor / gene transfer / positron emission tomography / adenovirus / raclopride / autoradiography / MRI / C-11 |
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| Research Abstract |
As the basic study of gene therapy, we investigated whether the expression of dopamine DィイD22ィエD2 receptor (DィイD22ィエD2R) gene injected into the rat striatum was evaluated in vivo by positron emission tomography (PET). preliminarily we established that the striatal DィイD22ィエD2R was evaluated by PET with ィイD111ィエD1C-labeled DィイD22ィエD2R-specific ligands by using normal rats and a rat model for striatal neurodegenerative diseases induced by striatal injection of quinolinic acid. To overcome the spatial resolution of PET camera, a technique of PET-MRI registration on the rat brain was developed.
PET measurement demonstrated that the uptake of three kinds of DィイD22ィエD2R-specific ligands, [ィイD111ィエD1C]raclopride, [ィイD111ィエD1C]nemonapride and [ィイD111ィエD1C]N-methylspiperone was higher in the striatum injected with the vectors for DィイD22ィエD2R than the contralateral striatum injected with a control vector 2-3 days after injection. The uptake of [ィイD111ィエD1C]SCH 23390, a dopamine DィイD21ィエD2 receptor
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specific ligand, or [ィイD111ィエD1C]β-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata, and co-injection of excess unlabeled raclopride inhibited the uptake of [ィイD111ィエD1C]raclopride, suggesting the PET signal reflects the DィイD22ィエD2R-specific gene-expression. These findings were confirmed by ex vivo and in vitro autoradiography. At day 16 the increased uptake of [ィイD111ィエD1C]raclopride declined to basal level, suggesting that the gene expression is temporary.
We concluded that PET imaging is capable of detecting adenovirus-mediated gene transfer in vivo. This technique represents a major advance over in vitro ARG analysis of DィイD22ィエD2R binding which must be done post-hoc. PET imaging permits in vivo analysis of the efficiency of DィイD22ィエD2R gene transfer that can be followed longitudinally and related to any functional changes being observed. Such imaging will prove highly valuable for assessment of gene transfer using this and similar vectors. Less
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[Publications] Ogawa O., Umegaki H., Ishiwata K., Asai Y., Ikari H., Oda K., Toyama H., Ingram D. K., Roth G. S., Iguchi A., Senda M.: "In vivo imaging of adenovirus-mediated overexpression of dopamine DィイD22ィエD2 receptors in rat striatum by positron emission tomography"NeuroReport. 11. 743-748 (2000)
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