Development of practical synthetic method of radiobromine-labeled peptides for PET imaging

• Project/Area Number: 15K09946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: Yamada Keiichi 群馬大学, 大学院理工学府, 准教授 (70323334)
• Research Collaborator: Watanabe Shigeki ; Hanaoka Hirofumi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: PET薬剤 / 生物活性ペプチド / 放射性臭素 / 標識合成 / PETイメージング / 環状ペプチド / 腫瘍標的化ペプチド / PET診断薬

Outline of Final Research Achievements

We developed facile synthetic method of radiobromine-labeled bioactive peptides via electrophilic desilylation. In this study, we synthesized bromine-77 labeled cyclic RGD peptide in good radiochemical yield.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した標識合成法は核医学的診断に資する新規放射性ペプチド薬剤の合成に適用できるため、腫瘍をはじめとする様々な疾病の非侵襲的診断やRI内用療法に基づく放射線治療への応用が期待される。また、放射性臭素は現在実用化されている放射性フッ素よりも半減期が長いため、遠隔地への標識化合物の輸送が実現できれば、RI製造設備を持たない医療機関でのPET検査などに利用できる可能性がある。

Research Products

• [Journal Article] A convenient and reproducible method for the synthesis of astatinated 4-[211At]astato-l-phenylalanine via electrophilic desilylation (2019)
  • Author(s): Watanabe Shigeki、Azim Mohammad Anwar-Ul、Nishinaka Ichiro、Sasaki Ichiro、Ohshima Yasuhiro、Yamada Keiichi、Ishioka Noriko S.
  • Journal Title: Organic & Biomolecular Chemistry Volume: 17 Issue: 1 Pages: 165-171
  • DOI: 10.1039/c8ob02394h
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 放射性ペプチド薬剤の標識合成と診断・治療への展開:現状と課題 (2019)
  • Author(s): 山田圭一
  • Journal Title: Bio Industry Volume: 36 Pages: 75-81
• [Journal Article] Synthesis and Characterization of Radiobromine-labeled Bioactive Peptides for Molecular Imaging (2018)
  • Author(s): Keiichi Yamada, Shigeki Watanabe, Ichiro Sasaki, Hirofumi Hanaoka, and Noriko S. Ishioka
  • Journal Title: Peptide Science 2017 Volume: -
  • Peer Reviewed
• [Journal Article] PET薬剤を指向した放射性ハロゲン標識化合物の開発：現状と課題 (2017)
  • Author(s): 山田圭一
  • Journal Title: Bio Clinica Volume: 32 Pages: 66-71
  • Peer Reviewed
• [Journal Article] Synthesis and properties of silylated phenylalanine derivatives (2016)
  • Author(s): K. Yamada, S. Watanabe, S. Watanabe, T. Takahashi, T. Moriguchi, H. Oku, N. S. Ishioka, and K. Shinozuka
  • Journal Title: Peptide Science 2015 Volume: 52 Pages: 93-94
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ケイ素―ハロゲン交換反応を用いた放射性臭素標識化合物合成に関する基礎的検討 (2018)
  • Author(s): 渡辺茂樹，山田圭一，佐々木一郎，石岡典子
  • Organizer: 第2回日本核医学会分科会放射薬品科学研究会/第18回放射性医薬品・画像診断薬研究会
• [Presentation] ケイ素ーアスタチン交換反応を用いたアスタチン標識アミノ酸誘導体の合成 (2018)
  • Author(s): 渡辺茂樹，Mohammad Anwar-UlAzim，西中一朗，佐々木一郎，大島康宏，山田圭一，石岡典子
  • Organizer: 第62回放射化学討論会
• [Presentation] 有機ケイ素前駆体を用いたアスタチン標識アミノ酸の合成 (2018)
  • Author(s): 渡辺茂樹，Mohammad Anwar-UlAzim，西中一朗，佐々木一郎，大島康宏，山田圭一，石岡典子
  • Organizer: 第５８回日本核医学会学術総会
• [Presentation] ケイ素-ハロゲン交換反応を利用した放射性臭素標識ペプチドの合成研究 (2017)
  • Author(s): 山田圭一, 渡辺茂樹, 佐々木一郎, 花岡宏史, 石岡典子
  • Organizer: 第17回放射性医薬品画像診断薬研究会
• [Presentation] 有機ケイ素前駆体を用いた放射性臭素標識アミノ酸誘導体の合成 (2017)
  • Author(s): 渡辺茂樹, 佐々木一郎, 山田圭一, 石岡典子
  • Organizer: 第57回日本核医学会学術総会
• [Presentation] ynthesis and Characterization of Radiobromine-labeled Bioactive Peptides for Molecular Imaging (2017)
  • Author(s): K. Yamada, S. Watanabe, I. Sasaki, H. Hanaoka, and N. S. Ishioka
  • Organizer: 第54回ペプチド討論会
• [Presentation] Synthesis and Biological Evaluation of N-Methylated Cyclic Pentapeptides against Malignant Breast Cancer Cell Lines (2016)
  • Author(s): K. Yamada, S. Rokudai, R. Kawabata, M. Nishiyama K. Shinozuka
  • Organizer: 3rd International Symposium of Gunma University Medical Innovation
  • Place of Presentation: Kiryu, Gunma
  • Int'l Joint Research
• [Presentation] Synthesis and properties of silylated phenylalanine derivatives and its application to bioactive cyclic peptides (2015)
  • Author(s): K. Yamada, S. Watanabe, S. Watanabe, S. Torii, N. S. Ishioka, and K. Shinozuka
  • Organizer: 2nd International Symposium of Gunma University Medical Innovation
  • Place of Presentation: Gunma University, Maebashi, Japan
  • Year and Date: 2015-12-08
  • Int'l Joint Research
• [Presentation] Synthesis and properties of silylated phenylalanine derivatives (2015)
  • Author(s): K. Yamada, S. Watanabe, S. Watanabe, T. Takahashi, T. Moriguchi, H. Oku, N. S. Ishioka, and K. Shinozuka
  • Organizer: 52nd Japanese Peptide Symposium
  • Place of Presentation: Hiratsuka City Hall, Hiratsuka, Japan
  • Year and Date: 2015-11-15
• [Presentation] Synthesis of a Radiobrominated Amino Acid Derivatives via Silicon-Bromine Exchange Reaction (2015)
  • Author(s): S. Watanabe, K. Yamada, S. Watanabe, H. Oku, T. Moriguchi, K. Shinozuka, N. S. Ishioka
  • Organizer: 21st International symposium on Radiopharmaceutical Sciences
  • Place of Presentation: Missouri, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Remarks] Dr. Yamada Homepage
  • URL: http://peptide-chem.chem-bio.st.gunma-u.ac.jp/yamada/yamada-index.html