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Development of fluorine-19 MRI probes to evaluate pathological features in Alzheimers disease

Research Project

Project/Area Number 25750159
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionShiga University of Medical Science

Principal Investigator

YANAGISAWA Daijiro  滋賀医科大学, 分子神経科学研究センター, 助教 (50581112)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアルツハイマー病 / フッ素MRI / 老人斑 / 神経原線維変化 / MRI / 診断法
Outline of Final Research Achievements

Fluorine-19 magnetic resonance imaging (19F MRI) could be a promising approach for imaging amyloid deposition in the brain. However, the required features of a 19F MRI probe for amyloid detection remain unclear. In the present study, we investigated a series of compounds as potent 19F probes that could prevent the reduction in MR signal when bound to amyloid plaques in the brain. We found that 6-(3’,6’,9’,15’,18’,21’-heptaoxa-23’,23’,23’-trifluorotricosanyloxy)-2-(4’-dimethylaminostyryl)benzoxazole (Shiga-X22), which has a trifluoroethoxy group with seven ethylene glycol groups in the PEG chain, showed significant 19F MR signals in the brains of APPswe/PS1dE9 double-transgenic mice, but not wild-type mice. This suggested that Shiga-X22 could be a useful 19F MRI probe for amyloid detection. Furthermore, we synthesized new probes for neurofibrillary tangles, which has a trifluoroethoxy group with different number of ethylene glycol groups in the PEG chain.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Synthesis and Tautomerism of Curcumin Derivatives and Related Compounds2014

    • Author(s)
      Taguchi H, Yanagisawa D, Morikawa S, Hirao K, Shirai N, Tooyama I
    • Journal Title

      Australian Journal of Chemistry

      Volume: 68 Issue: 2 Pages: 224-229

    • DOI

      10.1071/ch14464

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Curcumin derivative with substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PSI mice2014

    • Author(s)
      Yanagisawa D, Ibraham NF, Taguchi H, Morikawa S, Hirao K, Shirai N, Sogabe T, Tooyama I
    • Journal Title

      Neurobiol Aging

      Volume: 36 Issue: 1 Pages: 210-210

    • DOI

      10.1016/j.neurobiolaging.2014.07.041

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferred features of a fluorine-19 MRI probe foramyloid detection in the brain2014

    • Author(s)
      Yanagisawa D, Taguchi H, Ibrahim NF, Morikawa S, Shiino A, Inubushi T, Hirao K, Shirai N, Sogabe T, Toovama I
    • Journal Title

      J AIzhei mer's Dis

      Volume: 39 Issue: 3 Pages: 617-631

    • DOI

      10.3233/jad-131025

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Shiga-Y5 is a potential diagnostic and therapeutic agent for Alzheimer’s disease2015

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Ikuo Tooyama
    • Organizer
      新学術領域脳内環境-恒常性維持機構とその破綻-第2回若手研究者によるシンポジウム
    • Place of Presentation
      広島大学広仁会館
    • Year and Date
      2015-01-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] アルツハイマー病遺伝子改変マウスにおける新規クルクミン誘導体の治療効果の解析2014

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、Lina Wati Durani、田口弘康、遠山育夫
    • Organizer
      第33回日本認知症学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-29 – 2014-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Amyloid detection using fluorine-19 MRI in the transgenic mouse model of AD2014

    • Author(s)
      Daijiro Yanagisawa
    • Organizer
      18th MNRC International Symposium
    • Place of Presentation
      滋賀医科大学
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高磁場MR装置を利用したアルツハイマー病画像診断法の開発2014

    • Author(s)
      柳沢大治郎
    • Organizer
      2014年度創薬科学フロンティアシンポジウム
    • Place of Presentation
      京都薬科大学
    • Year and Date
      2014-11-23 – 2014-11-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Novel curcumin derivative with C-4 substituent inhibits amyloid pathology in APPswe/PS1dE9 mice2014

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Nor Faeizah Ibrahim, Lina Wati Durani, Shigehiro Morikawa, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Ikuo Tooyama
    • Organizer
      Society for Neuroscience’s 44th Annual Meeting
    • Place of Presentation
      Washington DC, アメリカ合衆国
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] クルクミン誘導体によるAβ凝集抑制効果とAβによる細胞障害軽減効果の解析2014

    • Author(s)
      柳沢大治郎、遠山育夫、Nor Faeizah Ibrahim、田口弘康
    • Organizer
      第11回認知症サプリメント研究会
    • Place of Presentation
      AP品川
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病治療効果を示す新規クルクミン誘導体の開発2014

    • Author(s)
      柳沢大治郎、Nor Faeizah Ibrahim、田口弘康、遠山育夫
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高磁場MR装置を利用したフッ素MRIアミロイドイメージングのためのstyrylbenzoxazole誘導体の開発2014

    • Author(s)
      柳沢大治郎、田口弘康、森川茂廣、椎野顯彦、犬伏俊郎、遠山育夫
    • Organizer
      第9回日本分子イメージング学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター
    • Year and Date
      2014-05-22 – 2014-05-23
    • Related Report
      2014 Annual Research Report 2013 Research-status Report
  • [Presentation] Required features of a fluorine-19 MRI probe for amyloid detection in the brain2013

    • Author(s)
      Daijiro Yanagisawa, Hiroyasu Taguchi, Shigehiro Morikawa, Akihiko Shiino, Toshiro Inubushi, Nor Faeizah Ibrahim, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Ikuo Tooyama
    • Organizer
      Alzheimer’s Association 2013 International Conference on Alzheimer’s Disease
    • Place of Presentation
      米国ボストン
    • Related Report
      2013 Research-status Report
  • [Presentation] アルツハイマー病画像診断を目的とした19F MRIによる脳内アミロイド斑の検出(その2)2013

    • Author(s)
      柳沢大治郎、田口弘康、森川茂廣、椎野顯彦、犬伏俊郎、Ibrahim Nor Faeizah、遠山育夫
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 神経難病のMR画像診断薬2014

    • Inventor(s)
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Holder
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-01-06
    • Related Report
      2013 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 神経難病のMR画像診断薬2013

    • Inventor(s)
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Holder
      遠山育夫、田口弘康、柳沢大治郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-202531
    • Filing Date
      2013-09-27
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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