Development of imaging probes for systemic amyloidosis diseases

• Project/Area Number: 15K19827
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Nagasaki University (2016); Kobe Pharmaceutical University (2015)
• Principal Investigator: HAGIMORI Masayori 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (40446125)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 全身性アミロイドーシス / 早期診断 / 核医学イメージングプローブ / 蛍光イメージングプローブ / 放射性ヨウ素標識体 / 治療モニタリング

Outline of Final Research Achievements

For diagnosis and monitoring therapeutic efficacy of systemic amyloidosis diseases, we planned to develop a nuclear imaging probe with similar binding affinities to a variety of amyloid fibrils and fluorescent probes with a selective binding affinity to a specific amyloid fibril. Radioiodine labelled compound [125I]1 based on the structure of thioflavine T showed similar binding affinities to SAA fibril and Aβ fibril. In AA amyloid model mice, considerable accumulation of radioactivity was observed in predilection sites of AA amyloid such as the spleen, kidney, and liver. In addition, we synthesized fluorescent probes with a selective binding affinity to a specific amyloid fibril by investigating substituent groups.

Research Products

• [Journal Article] 2-Pyridone-based fluorophores containing 4-dialkylamino-phenyl group: Synthesis and fluorescence properties in solutions and in solid state (2016)
  • Author(s): Masayori Hagimori, Yasuhiro Shigemitsu, Ryo Murakami, Kenichirou Yokota, Yasuhisa Nishimura, Naoko Mizuyama, Bo-Cheng Wang, Chen-Kuen Tai, San-Lang Wang, Tzenge-Lien Shih, Kuen-Da Wu, Junko Nagaoka, Takahiro Mukai, Shinichi Kawashima, Keisuke Kawashima, Yoshinori Tominaga et al
  • Journal Title: Dyes and Pigments Volume: 124 Pages: 196-202
  • DOI: 10.1016/j.dyepig.2015.09.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis of indeno [1,2-d]pyrimidin-5-ones and their fluorescence in solid state (2016)
  • Author(s): M. Hagimori, K. Yokota, A. Fukuda, Y. Nishimura, R. Satodani, B.C. Wang, H.H. Wei, S.L. Wang, Y. Shigemitsu, Y. Tominaga
  • Journal Title: Journal of Heterocyclic Chemistry Volume: ５３ Issue: 2 Pages: 414-420
  • DOI: 10.1002/jhet.887
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 全身性アミロイドーシス診断を目指した放射性ヨウ素標識化合物の体内動態評価 (2016)
  • Author(s): 山内 健生、萩森 政頼、平野 優里、向 高弘
  • Organizer: 第66回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪薬科大学（大阪府・大阪市）
  • Year and Date: 2016-10-15
• [Presentation] 蛍光性ベンゾチアゾール誘導体の合成及びアミロイドタンパク質に対する選択性の評価 (2015)
  • Author(s): 舩崎彩、村本華奈子、萩森政頼、向高弘
  • Organizer: 第65回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（富田林市）
  • Year and Date: 2015-10-17
• [Presentation] 全身性アミロイド―シスの核医学イメージングを目指した放射性ヨウ素標識化合物の開発 (2015)
  • Author(s): 萩森政頼、平野優里、山内健生、向高弘
  • Organizer: 第3回アミロイド―シス研究会学術集会
  • Place of Presentation: KKRホテル東京（東京都千代田区）
  • Year and Date: 2015-08-21