• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

In vivo PET measurement of expression of dopamine D2 receptor gene injected into rat striatum

Research Project

Project/Area Number 10558115
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY

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)

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)
伊刈 弘之  名古屋大学, 医学部, 医員
成相 直  東京医科歯科大学, 医学部, 助手 (00228090)
外山 比南子  財団法人, 東京都老人総合研究所・ポジトロン医学研究部門, 主任研究員 (50180188)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥12,200,000 (Direct Cost: ¥12,200,000)
Keywordsdopamine D2 receptor / gene transfer / positron emission tomography / adenovirus / raclopride / autoradiography / MRI / C-11 / アデノウィルス / ドパミン受容体
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 … More 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

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] K Ishiwata et al.: "Quantitative ex vivo and in vitro autoradiographyusing ^<11>C-labeled lignds and imaging plate : a study with a dopamine D2-like receptor ligand [^<11>C]nemonapride"Nuclear Medicine and Biology. 26. 291-296 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K Ishiwata et al.: "An alternative synthesis of [^<11>C]raclopride for routine use"Anals of Nuclear Medicine. 13. 195-197 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K Ishiwata et al.: "Comparison of three PET dopamine D2-like recepter ligands,[^<11>C]raclopride,[^<11>C]nemonapride and,[^<11>C]N-nothylspiperone,in rats."Anals of Nuclear Medicine. 13. 161-167 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K Ishiwata et al.: "In vivo binding of [^<11>C]nemonapride to sigma receptors in the cortex and cerebellum"Nuclear Medicine and Biology. 26. 624-631 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Hayakawa et al.: "A PET-MRI registration technique for PET studies of the rat brain"Nuclear Medicine and Biology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiwata K., Ogi N., Tanaka A. and Senda M.: "Quantitative ex vivo and in vitro receptor autoradiography using ィイD111ィエD1C-labeled ligands and an imaging plate: a study with a dopamine DィイD22ィエD2-like receptor ligand [ィイD111ィエD1C]nemonapride"Nucl. Med. Biol.. 26. 291-296 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiwata K., Ishii S. and Senda M.: "An alternative synthesis of [ィイD111ィエD1C]raclopride for routine use"Ann. Nucl. Med.. 13. 195-197 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiwata K., Hayakawa N., Ogi N., Oda K., Toyama H., Endo K., Tanaka A. and Senda M.: "Comparison of three PET dopamine DィイD22ィエD2-like receptor ligands, [ィイD111ィエD1C]raclopride, [ィイD111ィエD1C]nemonapride and [ィイD111ィエD1C]N-methylspiperone, in rats"Ann. Nucl. Med.. 13. 161-167 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiwata K. and Senda M.: "In vivo binding of [ィイD111ィエD1C]nemonapride to sigma receptors in the cortex and cerebellum"Nucl. Med. Biol.. 26. 627-631 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayakawa N., Uemura K., Ishiwata K., Shimada Y., Ogi N., Nagaoka T., Toyama H., Oda K., Tanaka A., Endo K. and Senda M.: "A PET-MRI registration technique for PET studies of the rat brain"Nucl. Med. Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Ishiwata et al.: "Quantitative ex vivo and in vitro autoradiography using ^<11>C-labeled ligands and an imaging plate : a study with a dopamine D_2-like receptor ligand [^<11>C]nemonapride"Nuclear Medicine and Biology. 26. 291-296 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Ishiwata et al.: "An alternative synthesis of [^<11>C] raclopride for routine use"Annals of Nuclear Medicine. 13. 195-197 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Ishiwata et al.: "Comparison of three PET dopamine D_2-like receptor ligands, [^<11>C] raclopride, [^<11>C] nemonapride and [^<11>C] N-methylspiperone, in rats"Annals of Nuclear Medicine. 13. 161-167 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Ishiwata et al.: "In vivo binding of [^<11>C] nemonapride to sigma receptors in the cortex and cerebellum"Nuclear Medicine and Biology. 26. 627-631 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Hayakawa et al.: "A PET-MRI registration technique for PET studies of the rat brain"Nuclear Medicine and Biology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ishiwata et al.: "Quantitatius oxvivo and in vitro autoradiogrophy using ^<11>C-labeled ligands and an imaging plate:a study with a dopamine D_2-like receptor ligand [^<11>C]nemonapride." Nuclear Modicine and Biology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Ishiwata et al.: "An alternatiue synthesis of [^<11>C]radopride foe routine use." Annals of Nuclear Medicine. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Isiwata et al.: "Comparison of three PET dopamine D_2-like receptor ligands,[^<11>C]radopride,[^<11>C]nemonapride and [^<11>C]N-methylspiperone,in rats." Annals of Nuclear Medicine. (in press).

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi