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PET measurement system as a biomarker of central nervous system pharmacological effect of drugs.

Research Project

Project/Area Number 16390350
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionInstitute of Biomedical Research and Innovation

Principal Investigator

SENDA Michio  Institute of Biomedical Research and Innovation, Department of Image-based Medicine, Director, 先端医療センタ研究所, 副所長 (00216558)

Co-Investigator(Kenkyū-buntansha) TOMINAGA Hideyuki  Institute of Biomedical Research and Innovation, Department of Image-based Medicine, Research Scientist, 分子イメージ研究グループ, 研究員 (00393348)
MAEDA Kiyoshi  Kobe University, School of Medicine, Professor, 大学院医学系研究科・精神神経科学, 教授 (80116251)
SAKAMOTO Setsu  Institute of Biomedical Research and Innovation, Department of Image-based Medicine, Senior Research Scientist, 分子イメージ研究グループ, 主任研究員 (40344402)
幸原 伸夫  神戸市立中央市民病院, 神経内科, 部長
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsPET / clinical pharmacology / histamine H1 receptor / doxepin / antihistmine / reproducibility / 動態解析 / 統計画像 / FDG / 脳糖代謝 / アルツハイマー病 / 軽度認知障害 / ドネペジル
Research Abstract

PET is useful for evaluating pharmacological effect of drugs although only a few clinical trials have been conducted in Japan due to poor environment both in technologies and regulations. We have established the so-called in-house GMP-based quality control according to the guidelines issued by the Japan Radioisotope Association (Version 2001) in the Institute of Biomedical Research and Innovation. An imaging CRO specializing in PET was established locally to support clinical trials using PET. An in-house license for the PET research nurse has also been established. Using these systems, a clinical study was conducted regarding PET measurement of the central nervous system pharmacological effect of a drug. Some antihistamines have a sedative effect as they enter the brain and block the histamine H1 receptor, which is difficult to evaluate in behavioral tests due to large variation but can be measured as H1 receptor occupancy using PET with C-11 labeled doxepin. Olopatadine is a slightly sedative antihistamine, but the sedative effect wears off after repeated medication. In the present study, H1 receptor binding potential (BP) was measured with PET on 17 subjects with perennial nasal allergy at baseline, at the initial dose of olopatadine, and at another dose after repeated administration of olopatadine for four weeks. The BP of the frontal cortex under the initial single dose was slightly lower than the baseline, but it showed a marked decrease following 4-week medication, which suggests down regulation of H1 receptor possibly due to increased endogenous histamine level and may be related to the wearing off phenomenon. The results indicate that it is possible and plausible to evaluate the central nervous system effect of a drug and its repeated administration on the receptor using PET, which may be useful for drug development.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2007 2006 2005 2004

All Journal Article (23 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Clinical value of manual fusion of PET and CT images in patients with suspected recurrent colorectal cancer.2007

    • Author(s)
      Nakamoto Y, Sakamoto S, Okada T, Senda M, Higashi T, Saga T, Togashi K
    • Journal Title

      Am J Roentgenol 188(1)

      Pages: 257-67

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 二次元および三次元PET収集における雑音等価計数と再構成画像の画質の評価2006

    • Author(s)
      松本圭一, 清水敬二, 北村圭司, 渡辺英治, 村瀬研也, 千田道雄
    • Journal Title

      日本放射線技術学会雑誌 62(8)

      Pages: 1111-1118

    • NAID

      110004788652

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Development of a flexible end-shield using tungsten curtains for 3D PET.2006

    • Author(s)
      Yamamoto Y, Sakamoto S, Matsumoto K, Senda M
    • Journal Title

      IEEE Trans Nuclear Sci 53(5)

      Pages: 2671-2674

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Performance of list mode data acquisition with ECAT EXACT HR and ECAT EXACT HR+ positron emission scanners.2006

    • Author(s)
      Watabe H, Matsumoto K, Senda M, Iida H.
    • Journal Title

      Ann Nucl Med 20(3)

      Pages: 189-194

    • NAID

      10018776193

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Performance characteristics of a new 3-dimensional continuous-emission and spiral-transmission high-sensitivity and high-resolution PET camera evaluated with the NEMA NU 2-2001 standard.2006

    • Author(s)
      Matsumoto K, Kitamura K, Mizuta T, Tanaka K, Yamamoto S, Sakamoto S, Nakamoto Y, Amano M, Murase K, Senda M
    • Journal Title

      J Nucl Med 47(1)

      Pages: 83-90

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Usefulness of L- [methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      Nariai T, Tanaka Y, Senda M
    • Journal Title

      J Neurosurg 103(3)

      Pages: 498-507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      NariaiT, TanakaY, Senda M
    • Journal Title

      J Neurosurg 103(3)

      Pages: 498-507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An intra-operative positron probe with background rejection capability for FDG-guided surgery.2005

    • Author(s)
      Yamamoto S, Matsumoto K, Sakamoto S, Tarutani K, Minato K, Senda
    • Journal Title

      Ann Nucl Med 19(1)

      Pages: 23-28

    • NAID

      10018370261

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Severe haemodynamic stress in selected subtypes of patients with moyamoya disease : a positron emission tomography study.2005

    • Author(s)
      Nariai T, Matsushima Y, ImaeS, Tanaka Y, Ishii K, Senda M, Ohno K.
    • Journal Title

      J Neurol Neurosurg Psychiatry 76(5)

      Pages: 663-669

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Accuracy of image fusion using a fixation device for whole-body cancer imaging.2005

    • Author(s)
      Nakamoto Y, Sakamoto S, Okada T, Matsumoto K, Minota E, Senda M
    • Journal Title

      Am J Roentgenol 184(6)

      Pages: 1960-1966

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Investigation of single, random, and true counts from natural radioactivity in LSO-based clinical PET2005

    • Author(s)
      Yamamoto S, Horii H, Hurutani M, Matsumoto K, Senda M
    • Journal Title

      Ann Nucl Med 19(2)

      Pages: 109-114

    • NAID

      10018370013

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.2005

    • Author(s)
      Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishiwata K, Senda M
    • Journal Title

      J Neurosurg 103(3)

      Pages: 498-507

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Database of normal human CBF, CBV, OEF, CMRO2 measured by PET with 150-labelled CO2/H2O, CO. 02 : a multicentre study in Japan.2004

    • Author(s)
      Ito H, Kanno I, Senda M
    • Journal Title

      Eur J Nucl Med Mol Imaging. 31(5)

      Pages: 635-643

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Validation of anatomical standardization of FDG PET images of normal brain : comparison of SPM and NEUROSTAT.2004

    • Author(s)
      Hosaka K, Ishii K, Senda M
    • Journal Title

      Eur J Nucl Med Mol Imaging 32(1)

      Pages: 92-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Performance characteristics of a new 3-dimensional continuous-emission and spiral-transmission high-sensitivity and high-resolution PET camera evaluated with the NEMA NU 2-2001 standard.2004

    • Author(s)
      Matsumoto K, Kitamura K, Mizuta T, Senda M
    • Journal Title

      J Nucl Med 47(1)

      Pages: 83-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Database of normal human CBF, CBV, OEF, CMR02 measured by PET with 150-labelled CO2/H2O, CO, 02 : a multicentre study in Japan.2004

    • Author(s)
      Ito H, Kanno I, Senda M
    • Journal Title

      Eur J Nucl Med Mol Imaging. 31(5)

      Pages: 635-643

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Validation of anatomical standardization of FDG PET images of normal brain : comparison of SPM and NEUROSTAT.2004

    • Author(s)
      Hosaka K, Ishii K, Senda M
    • Journal Title

      Eur J Nucl Med Mol Imaging. 32(1)

      Pages: 92-97

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Performance characteristics of a new 3-dimensional continuous-emission and spiral-transmission high-sensitivity and high-resolution PET camera evaluated with the NEMA NU 2-2001 standard.2004

    • Author(s)
      Matsumoto K, KitamuraK, MizutaT, Senda M
    • Journal Title

      J Nucl Med. 47(1)

      Pages: 83-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Database of normal human CBF, CBV, OEF, CMRO2 measured by PET with 150-labelled CO2/H2O, CO, O2 : a multicentre study in Japan.2004

    • Author(s)
      Ito, H, Kanno, I,..., Senda, M.
    • Journal Title

      Eur J Nucl Med Mol Imaging 31(5)

      Pages: 635-643

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Midbrain hypometabolism as early diagnostic sign for progressive Supranuclear palsy.2004

    • Author(s)
      Mishina K, Ishii K,.., Senda M
    • Journal Title

      Acta Neurol Scand 110

      Pages: 128-135

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Oscillopsia associated with dysfunction of visual cortex.2004

    • Author(s)
      Suzuki Y, Kiyosawa M,.., Senda M
    • Journal Title

      Jpn J Ophthalmol. 48(2)

      Pages: 128-132

    • NAID

      80016713700

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Optimum threshold setting for a positron-sensitive probe with background rejection capability.2004

    • Author(s)
      Yamamoto S, Matsumoto K, Senda M.
    • Journal Title

      Ann Nucl Med. 18(3)

      Pages: 251-256

    • NAID

      10017669769

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Validation of anatomical standardization of FDG PET images of normal brain : comparison of SPM and NEUROSTAT.2004

    • Author(s)
      Hosaka K, Ishii K,.., Senda M.
    • Journal Title

      Eur J Nucl Med Mol Imaging 32(1)

      Pages: 92-97

    • Related Report
      2004 Annual Research Report
  • [Book] 「マイクロドース試験 理論と実践」の第4章2 PETの計測原理と精度管理(杉山雄一、栗原千絵子編)2007

    • Author(s)
      千田道雄
    • Publisher
      株式会社じほう
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 杉山雄一, 栗原千絵子編「マイクロドース試験 理論と実践」の第4章2 PETの計測原理と精度管理2007

    • Author(s)
      千田道雄
    • Publisher
      株式会社じほう
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 断層撮影装置,それを備えた撮影システム並びに撮影データ取得方法2007

    • Inventor(s)
      千田道雄ほか
    • Industrial Property Rights Holder
      先端医療振興財団ほか
    • Industrial Property Number
      2007-001469
    • Filing Date
      2007-01-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 断層撮影装置、それを備えた撮影システム並びに撮影データ取得方法2007

    • Inventor(s)
      千田道雄ほか
    • Industrial Property Rights Holder
      先端医療振興財団ほか
    • Industrial Property Number
      2007-001469
    • Filing Date
      2007-01-09
    • Related Report
      2006 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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