Development of amyloid imaging using fluorine-MRI

2013 Fiscal Year Final Research Report

• Project/Area Number: 22300153
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TOOYAMA Ikuo 滋賀医科大学, 分子神経科学研究センター, 教授 (20207533)
• Co-Investigator(Kenkyū-buntansha): TAGUCHI Hiroyasu 滋賀医科大学, 分子神経科学研究センタ ー, 特任教授 (90102912)
• Co-Investigator(Renkei-kenkyūsha): INUBUSHI Toshiro 滋賀医科大学, MR医学総合研究センタ ー, 教授 (20213142)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 神経科学 / アルツハイマー病 / 核磁気共鳴画像 / 分子イメージング / 画像診断

Research Abstract

The aim of this study is to develop amyloid imaging using 19F MRI. We have developed a novel 19F-containing curcumin derivative (named FMeC1 or Shiga-Y5) as a potential 19F MRI probe for amyloid imaging. When Tg2576 mice, a transgenic mouse model of Alzheimer's disease, at 20-22 months of age were peripherally injected with FMeC1, dose-dependent increasing in the level of 19F signal was observed in 19F MR spectra obtained from the whole head. 19F MR image showed remarkable levels of 19F signal in the brain of Tg2576 mice after the injection of FMeC1 at a dose of 200 mg/kg. There are no significant 19F signals in the brain of FMeC1-injected wild-type mice. Histological analysis of FMeC1-injected Tg2576 mouse brain showed strong fluorescence signal for FMeC1, and most of this signal was co-localized with beta-amyloid peptide-immunoreactivity. These results suggest the potential benefit of 19F MRI with FMeC1 for amyloid imaging.

Research Products

• [Journal Article] Preferred features of a fluorine-19 MRI probe foramyloid detection in the brain (2014)
  • 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 Pages: 617-631
  • DOI: 10.3233/JAD-131025
  • Peer Reviewed
• [Journal Article] Distinct localization of peripheral and central types of choline acetyltransfer ase in the rat cochlea (2013)
  • Author(s): Kitanishi T, Aimi Y, Kitano H, Suzuki M, Kimura H, Saito A, Shimizu T, Tooyama I
  • Journal Title: Acta Histochem Cytochem Volume: 46 Pages: 145-152
  • DOI: 10.1267/ahc.13021
  • Peer Reviewed
• [Journal Article] In Vivo Detection of Copper Ions by Magnetic Resonance Imaging Using a Prion-Based Contrast Agent (2012)
  • Author(s): Makino S, Umemoto T, Yamada H, Yezdimer EM, Toovama I
  • Journal Title: Appl Biochem Biotechnol Volume: 168 Pages: 504-518
  • DOI: 10.1007/s12010-ol2-9792-7
  • Peer Reviewed
• [Journal Article] Correlation of Aβ deposition in the nasal cavity with the formation of senile plaques in the brain of a transgenic mouse model of Alzheimer's disease (2012)
  • Author(s): Kameshima N, Nanjou T, Fukuhara T, Yan agisawa D, Tooyama I
  • Journal Title: Neurosci Lett Volume: 513 Pages: 166-169
  • DOI: 10.1016/j.neulet.2012.02.026
  • Peer Reviewed
• [Journal Article] アルツハイマー病診断のための新規MR造影剤の開発 (2012)
  • Author(s): 遠山育夫
  • Journal Title: 神戸医師会報 Volume: 2月号 Pages: 51-57
• [Journal Article] 核磁気共鳴画像によるアミロイドイメージング用トレーサー (2011)
  • Author(s): 遠山育夫, 田口弘康、柳沢大治郎
  • Journal Title: 鳥取医療 Volume: 4 Pages: 68-74
  • Peer Reviewed
• [Journal Article] In vivo detection of amyloid b deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer's disease (2011)
  • Author(s): Yanagisawa D, Amatsubo T, Morikawa S, Taguchi H, Umshitania M, Shirai N, Hirao K, Shiino A, Inubushid T, Toovama I
  • Journal Title: Neuroscience Volume: 184 Pages: 120-127
  • DOI: 10.1016/j.neuroscience.2011.03.071
  • Peer Reviewed
• [Journal Article] Curcuminoid binds to amyloid β(1-42)oligomer and fibrilJ (2011)
  • Author(s): Yanagisawa H, Taguchi H, Yamamoto A, Shirai N, Hirao K, Toovama I
  • Journal Title: AIzheimer Dis Volume: 24 (supple 2) Pages: 33-42
  • DOI: 10.3233/JAD-2011-102100
  • Peer Reviewed
• [Presentation] Preferred features of a fluorine-19 MRI probe for amyloid detection in the brain (2013)
  • Author(s): Yanagisawa D, Taguchi H, Morikawa S, Inubushi T, Ibrahim NF, Hirao K, Shirai N, Sogabe T, Toovama I
  • Organizer: 第15回国際アルツハイマー病会議(AAIC2013)
  • Place of Presentation: 米国ボストン市
  • Year and Date: 20130713-18
• [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): Yanagisawa D, Morikawa S, Taguchi H, Shiino A,Inubushi T, Ibrahim NF, Toovama I
  • Organizer: 第36回日本神経科学会学術大会(Neuro2013)
  • Place of Presentation: 京都
  • Year and Date: 20130620-23
• [Presentation] A novel 19F MRI probe for detecting amyloid plaques in Alzheiemr's disease (2012)
  • Author(s): Tooyama I
  • Organizer: The 5th Harbin International Neurosugery Conference
  • Place of Presentation: 中国、ハルビン
  • Year and Date: 20120620-23
  • Invited
• [Presentation] クルクミン骨格をもつ高磁場MRI用アミロイドイメージング試薬の検討 (2012)
  • Author(s): 遠山育夫
  • Organizer: 第53回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 20120522-25
• [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の検出 (2011)
  • Author(s): 柳沢大治郎、森川茂廣、田口弘康、椎野顕彦、犬伏俊郎、遠山育夫
  • Organizer: 第34回日本神経科学会学術大会(Neuro2011)
  • Place of Presentation: 横浜市
  • Year and Date: 20110914-17
• [Presentation] Curcumin binding activity to B-amyloid oligomer (2011)
  • Author(s): Yanagisawa D, Shirai N, Amatsubo T, Taguchi H, Hirao K, Urushitani M, Morikawa S, Inubushi T, Wada Y, Wada K, Yamamoto A, Tooyama I
  • Organizer: 第13回国際アルツハイマー病会議(ICAD2011)
  • Place of Presentation: フランスパリ市
  • Year and Date: 20110716-21
• [Presentation] クルクミンのケトエノール互変異性とアミロイド親和性を利用したアルツハイマー病診断薬の検討 (2011)
  • Author(s): 遠山育夫、柳沢大治郎、田口弘康
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20110518-20
• [Presentation] アルツハイマー病とクルクミン (2011)
  • Author(s): 遠山育夫
  • Organizer: 第5回認知症サプリメント研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-10
  • Invited
• [Presentation] Binding form of curcumin derivatives to B-amyloid aggregates (2010)
  • Author(s): Ynagisawa D, Shirai N, Amatsubo T, Taguchi H, Hirao K, Urushitani M, Morikawa S, Inubushi T, Wada Y, Wada K, Yamamoto A, Tooyama I
  • Organizer: 第12回国際アルツハイマー病会議(ICAD2010)
  • Place of Presentation: 米国ホノルル市
  • Year and Date: 20100710-15
• [Remarks]
  • URL: http://ben.shiga-med.ac.jp/~hqmnran/6
• [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: 滋賀医科大学
  • Industrial Property Rights Type: 特許出願
  • Industrial Property Number: 特願2013-001948
  • Filing Date: 2013-01-09
• [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: 滋賀医科大学
  • Industrial Property Rights Type: 特許出願
  • Industrial Property Number: 特願2013-202531
  • Filing Date: 2013-09-27