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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

Research Project

Project/Area Number 13557077
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Radiation science
Research InstitutionTokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare

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)

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)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥6,400,000 (Direct Cost: ¥6,400,000)
KeywordsSigma receptor / Positron emission tomography / Alzheimer's disease / Parkinson's disease / Schizophrenia / Receptor occupancy / P-glycoprotein / Tumor diagnosis / 加齢 / 神経変性疾患 / 脳腫瘍
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Ishiwata K., et al.: "[^<11>C]Raclopride binding was reduced in vivo by sigma1 receptor ligand SA4503 in the mouse brain, while [^<11>C]SA4503 binding was not by raclopride."Nuclear Medicine and Biology. 28・7. 787-792 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K., et al.: "Mapping of CNS sigma1 receptors in the conscious monkey : preliminary PET study with [^<11>C]SA4503."Synapse. 40・3. 235-237 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Elsinga PH., et al.: "Synthesis and evaluation of [^<18>F]fluoroethyl SA4503 as a PET ligand for the sigma receptor."Synapse. 43・4. 259-267 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang W.F., et al.: "Visualization of sigma, receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography."Experimental Eye Research. 75・6. 723-730 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K., et al.: "Different brain kinetics of two sigma1 receptor ligands, [^3H](+)-pentazocine and [^<11>C]SA4503, by P-glycoprotein modulation."Synapse. 48・2. 80-86 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K., et al.: "Age-related changes of the binding of [^3H]SA4503 to sigma_1 receptors in the rat brain."Annals of Nuclear Medicine. 17・2. 73-77 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K., et al.: "An increase of sigma, receptors in the aged monkey brain."Neurobiology and Aging. 24・5. 745-752 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K., et al.: "Synthesis and evaluation of ^<11>C- and ^<18>F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies."Nuclear Medicine and Biology. 30・3. 273-284 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K, et al.: "Sigma, and dopamine D_2 receptors occupancy in the mouse brain after a single administration of haloperidol and two dopamine D_2-like receptor ligands."Nuclear Medicine and Biology. 30・4. 429-434 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Elsinga PH, et al.: "Evaluation of [^<18>F]fluorinated sigma receptor ligands in the conscious monkey brain."Synapse. 52・1. 29-37 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K., Ishiwata K.: "Improved synthesis of [^<11>C]SA4503, [^<11>C]MPDX and [^<11>C]TMSX by use of [^<11>C]methyl triflate."Annals of Nuclear Medicine. 18・2. 165-168 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang FW, et al.: "Investigation of the use of positron emission tomography for neuroreceptor imaging in rabbit eyes."Ophthalic Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WE, et al.: "Investigation of the use of positron emission tomography for neuroreceptor imaging in rabbit eyes."Ophthalmol Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K, Ishiwata K.: "Improved synthesis of [^<11>C]SA4503,[^<11>C]MPDX and [^<11>C]TMSX by use of [^<11>C]methyl triflate."Ann Nucl Med. 18(2). 165-168 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Elsinga PH, et al.: "Evaluation of [^<18>F]fluorinated sigma receptor ligands in the conscious monkey brain."Synapse. 52(1). 29-37 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K, et al.: "An increase of sigma_1 receptors in the aged monkey brain."Neurobiol Aging. 24(5). 745-752 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K, et al.: "Sigma_1 and dopamine D_2 receptors occupancy in the mouse brain after a single administration of haloperidol and two dopamine D_2-like receptor ligands."Nucl Med Biol. 30(4). 429-434 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K, et al.: "Age-related changes of the binding of [^3H]SA4503 to sigma_1 receptors in the rat brain."Ann Nucl Med. 17(1). 73-77 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K, et al.: "Synthesis and evaluation of ^<11>C-and ^<18>F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies."Nucl Med Biol. 30(3). 273-284 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K, et al.: "Different brain kinetics of two sigma_1 receptor ligands [^3H](+)-pentazocine and [^<11>C]SA4503 by P-glycoprotein modulation."Synapse. 48(2). 80-86 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang WF, et al.: "Visualization of sigma_1 receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography."Exp Eye Res. 75(6). 723-730 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Elsinga PH, et al.: "Synthesis and evaluation of [^<18>F]fluoroethyl SA4503 as a PET-ligand for the sigma receptor."Synapse. 43(4). 259-267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K, et al.: "[^<11>C]Raclopride binding was reduced in vivo by sigma_1 receptor ligand SA4503 in the mouse brain, while [^<11>C]SA4503 binding was not by raclopride."Nucl Med Biol. 28(7). 787-792 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiwata K, et al.: "Mapping of CNS sigma_1 receptors in the conscious monkey : a preliminary PET study with [^<11>C]SA4503."Synapse. 40(4). 235-237 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawamura K., et al.: "An increase of sigma_1 receptors in the aged monkey brain."Neurobiology and Aging. 24・5. 745-752 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawamura K., et al.: "Synthesis and evaluation of ^<11>C-and ^<18>F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies."Nuclear Medicine and Biology. 30・3. 273-284 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Elsinga PH, et al.: "Evaluation of[^<18>F]fluorinated sigma receptor ligands in the conscious monkey brain."Synapse. 52・1. 29-37 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawamura K., et al.: "Improved synthesis of[^<11>C]SA4503,[^<11>C]MPDX and[^<11>C]TMSX by use of[^<11>C]methyl triflate."Annals of Nuclear Medicine. 30・3(印刷中). 273-284 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Elsinga P.H., et al.: "Synthesis and evaluation of [^<18>F]fluoroethyl SA4503 as a PET-ligand for the sigma receptor"Synapse. 43・4. 259-267 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wang W.F., et al.: "Visualization of sigma_1 receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography"Experimental Eye Research. 75・6. 723-730 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura K., et al.: "Different brain kinetics of two sigma1 receptor ligands, [^3H](+)-pentazocine and [^<11>C]SA4503, by P-glycoprotein modulation"Synapse. 48・2. 80-86 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishiwata K., et al.: "Age-related changes of the binding of [^3H]SA4503 to sigma_1 receptors in the rat brain"Annals of Nuclear Medicine. 17・7. 73-77 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura K., et al.: "An increase of sigma_1 receptors in the aged monkey brain"Neurobiology and Aging. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura K., et al.: "Synthesis and evaluation of ^<11>C-and ^<18>F-labeled 1-[2-(4-alkoxy-3-methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines as sigma receptor ligands for positron emission tomography studies"Nuclear Medicine and Biology. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishiwata K., et al.: "[^<11>C]Raclopride binding was reduced in vivo by sigmal receptor ligand SA4503 in the mouse brain, while [^<11>C]SA4503 binding was not by raclopride."Nuclear Medicine and Biology. 28・7. 787-792 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishiwata K., et al.: "Mapping of CNS sigmal receptors in the conscious monkey: preliminary PET study with [^<11>C]SA4503."Synapse. 40・3. 235-237 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Elsinga P.H., et al.: "Synthesis and evaluation of [^<18>F]fluoroethyl SA4503 as a PET-ligand for the sigma receptor."Synapse. 43・4. 259-267 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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