Development of small molecular radiolabeled probes for nuclear medical imaging of unstable plaques

• Project/Area Number: 24591813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Cardiovascular Center Research Institute (2014); Kyoto University (2012-2013)
• Principal Investigator: TEMMA TAKASHI 独立行政法人国立循環器病研究センター, 研究所, 室長 (90378787)
• Co-Investigator(Kenkyū-buntansha): SAJI Hideo 京都大学, 薬学研究科, 教授 (40115853) ; SHIOMI Masashi 神戸大学, 医学研究科, 准教授 (50226106)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 放射性医薬品 / 動脈硬化イメージング / 不安定プラーク

Outline of Final Research Achievements

This study aimed to develop small molecular radiolabeled probes for imaging Fatty Acid Binding Protein 4 (FABP4) and Matrix Metalloproteinase 12 (MMP12) in unstable plaques since FABP4 and MMP12 are promising candidates for molecular targeted therapy of atherosclerosis. 125I-TAP1 with triazolopyrimidine structure showed high FABP4 affinity and selectivity but showed high nonspecific accumulation in vitro. 18F-FTAP1 showing lower hydrophobicity rather than 125I-TAP1 maintained high affinity and selectivity toward FABP4 and succeeded in decrease of nonspecific accumulation in vitro. Besides, 18F-FTAP1 enabled in vivo imaging of FABP4 expression in mice by microPET/CT.

Research Products

• [Journal Article] Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer (2015)
  • Author(s): Temma T, Nishigori K, Onoe S, Sampei S, Kimura I, Ono M, Saji H
  • Journal Title: Nucl Med Biol Volume: 42 Issue: 2 Pages: 184-191
  • DOI: 10.1016/j.nucmedbio.2014.10.006
  • NAID: 120005539357
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of a Radioiodinated Triazolopyrimidine Probe for Nuclear Medical Imaging of Fatty Acid Binding Protein 4 (2014)
  • Author(s): Nishigori K, Temma T, Onoe S, Sampei S, Kimura I, Ono M, Saji H
  • Journal Title: PLOS ONE Volume: 印刷中 Issue: 4 Pages: e94668-e94668
  • DOI: 10.1371/journal.pone.0094668
  • Peer Reviewed
• [Journal Article] Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques (2013)
  • Author(s): Nishigori K, Temma T, Yoda K, Onoe S, Kondo N, Shiomi M, Ono M, Saji H.
  • Journal Title: Nuclear Medicine and Biology Volume: 40 Issue: 1 Pages: 97-103
  • DOI: 10.1016/j.nucmedbio.2012.08.002
  • Peer Reviewed
• [Presentation] Development of a novel radiofluorinated probe for PET imaging of fatty acid binding protein 4 in glioblastoma (2014)
  • Author(s): Temma T, Nishigori K, Kimura I, Ono M, Saji H
  • Organizer: XIII Turku PET Symposium
  • Place of Presentation: Turku (Finland)
  • Year and Date: 2014-05-24 – 2014-05-27
• [Presentation] A novel imaging probe targeting fatty acid binding protein-4 for evaluation of glioblastoma malignancy (2013)
  • Author(s): Nishigori K, Temma T, Ono M, Saji H
  • Organizer: Society of Nuclear Medicine 60th Annual Meeting
  • Place of Presentation: Vancouver, BC (Canada)
• [Presentation] Fatty acid binding protein-4イメージングプローブの開発：神経膠芽腫モデルマウスを用いた評価 (2013)
  • Author(s): 西郡寛太郎、天滿 敬、小野正博、佐治英郎
  • Organizer: 第53回日本核医学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] Fatty acid binding protein-4を標的としたトリアゾロピリミジン骨格を母体とする動脈硬化イメージングプローブの開発 (2012)
  • Author(s): 西郡寛太郎、天滿 敬、小野正博、佐治英郎
  • Organizer: 第10回次世代を担う若手のためのフィジカル・ファーマフォーラム
  • Place of Presentation: ホテル平安の森（京都府）
• [Presentation] Fatty acid binding protein-4を標的とした動脈硬化イメージングのための新規低分子プローブの開発 (2012)
  • Author(s): 西郡寛太郎、天滿 敬、小野正博、佐治英郎
  • Organizer: 第7回日本分子イメージング学会総会・学術集会
  • Place of Presentation: アクトシティ浜松コングレスセンター（静岡県）
• [Presentation] 動脈硬化の質的診断のための酸化LDL結合性核医学分子イメージングプローブ開発 (2012)
  • Author(s): 天滿 敬、西郡寛太郎、依田敬子、塩見雅志、小野正博、佐治英郎
  • Organizer: 第1回ウサギバイオサイエンス研究会
  • Place of Presentation: 宮崎観光ホテル（宮崎県）
• [Presentation] Development of a radioiodinated short peptide probe for selectively imaging oxidized LDL in atherosclerotic plaques (2012)
  • Author(s): Temma T, Nishigori K, Yoda K, Shiomi M, Ono M, Saji H
  • Organizer: Society of Nuclear Medicine 59th Annual Meeting
  • Place of Presentation: Miami Beach, Florida (United States of America)
• [Patent(Industrial Property Rights)] トリアゾロピリミジン誘導体化合物 (2013)
  • Inventor(s): 佐治英郎、天滿 敬、小野正博、関 育也
  • Industrial Property Rights Holder: 佐治英郎、天滿 敬、小野正博、関 育也
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-094993
  • Filing Date: 2013-04-30
• [Patent(Industrial Property Rights)] 不安定プラークへの選択性集積性に優れる化合物 (2012)
  • Inventor(s): 佐治英郎、小野正博、天滿敬、関育也
  • Industrial Property Rights Holder: 佐治英郎、小野正博、天滿敬、関育也
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-110965
  • Filing Date: 2012-05-14