Development of the high-sensitive imaging method for HIF-1-active hypoxic tumors based on the metabolic trapping approach

• Project/Area Number: 21791187
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: UEDA Masashi Kyoto University, 医学研究科, 助教 (40381967)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 放射性医薬品 / 分子イメージング / 低酸素 / HIF-1 / 代謝捕捉

Research Abstract

Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumor progression and in the development of resistance to radiotherapy. I designed a novel fusion protein (POTK) consisting of a protein transduction domain, herpes simplex virus type 1 thymidine kinase, and an essential part of the oxygen-dependent degradation domain of HIF-1 α that confers the same oxygen-dependent regulation as HIF-1α on POTK. I demonstrated that POTK and [^<123>I]FIAU, which is metabolized by POTK and trapped intracellularly, is potential probes for high-sensitive imaging of HIF-1-active regions in tumors.

Research Products

• [Journal Article] PET Imaging of Hypoxia-Inducible Factor-1-Active Tumor Cells with Pretargeted Oxygen-Dependent Degradable Streptavidin and a Novel ^<18>F-Labeled Biotin Derivative (2011)
  • Author(s): Kudo T, Ueda M, Konishi H, Kawashima H, Kuge Y, Mukai T, Miyano A, Tanaka S, Kizaka-Kondoh S, Hiraoka M, Saji H
  • Journal Title: Mol Imaging Biol Volume: (印刷中)
  • NAID: 120003824938
  • Peer Reviewed
• [Journal Article] Rapid detection of hypoxia-inducible factor-l-active tumours : pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-lalpha. (2010)
  • Author(s): Ueda M, Kudo T, Kuge Y, Mukai T, Tanaka S, Konishi H, Miyano A, Ono M, Kizaka-Kondoh S, Hiraoka M, Saji H.
  • Journal Title: Eur J Nucl Med Mol Imaging. 37 Pages: 1566-74
  • Peer Reviewed
• [Journal Article] Rapid detection of hypoxia-inducible factor-1-active tumours : pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1alpha (2010)
  • Author(s): Ueda M, Kudo T, Kuge Y, Mukai T, Tanaka S, Konishi H, Miyano A, Ono M, Kizaka-Kondoh S, Hiraoka M, Saji H
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 37 Pages: 1566-74
  • NAID: 120002511114
  • Peer Reviewed
• [Journal Article] PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel 18^F-labeled biotin derivative.
  • Author(s): Kudo T, Ueda M, Konishi H, Kawashima H, Kuge Y, Mukai T, Miyano A, Tanaka S, Kizaka-Kondoh S, Hiraoka M, Sail H.
  • Journal Title: Mol Imaging Biol. (in press)
  • NAID: 120003824938
  • Peer Reviewed
• [Presentation] HIF-1存在低酸素腫瘍イメージングのためのRI/蛍光デュアル標識タンパク質プローブの開発 (2011)
  • Author(s): 上田真史, 他
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 札幌
  • Year and Date: 2011-01-30
• [Presentation] HIF-1存在低酸素腫瘍イメージングのためのRI/蛍光デュアル標識タンパク質プローブの開発 (2011)
  • Author(s): 上田真史、宮野梓、工藤喬、小川京、小野正博、近藤科江、佐治英郎
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 北海道大学、札幌
  • Year and Date: 2011-01-30
• [Presentation] 高精度核医学分子イメージングのための放射性プローブの体内動態の化学制御法の開発:腫瘍低酸素領域のプレターゲットPETイメージング法 (2010)
  • Author(s): 上田真史, 他
  • Organizer: 第60回日本薬学会近畿支部総会・大会
  • Place of Presentation: 枚方
  • Year and Date: 2010-10-30
• [Presentation] 高精度核医学分子イメージングのための放射性プローブの体内動態の化学制御法の開発 : 腫瘍低酸素領域のプレターゲットPETイメージング法 (2010)
  • Author(s): 上田真史、工藤喬、小西宏明、小川京、河嶋秀和、小野正博、向高弘、久下裕司、近藤科江、平岡眞寛、佐治英郎
  • Organizer: 第60回日本薬学会近畿支部総会・大会
  • Place of Presentation: 摂南大学、枚方
  • Year and Date: 2010-10-30
• [Presentation] Pretargeted PET imaging of hypoxia-inducible factor-l-active tumors with an oxygen-dependent degradable streptavidin and a 18^F-labeled biotin derivative. (2010)
  • Author(s): Ueda M, et al.
  • Organizer: 2010 World Molecular Imaging Congress.
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2010-09-08
• [Presentation] Pretargeted PET imaging of hypoxia-inducible factor-1-active tumors with an oxygen-dependent degradable streptavidin and a ^<18>F-labeled biotin derivative (2010)
  • Author(s): Ueda M, Kudo T, Konishi H, Kawashima H, Kuge Y, Mukai T, Ono M, Kizaka-Kondoh S, Hiraoka M, Saji H
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-09-08
• [Presentation] Tumor pretargeting in mice using an oxygen-dependent degradable streptavidin and a radioiodinated biotin: comparison between autoradiography and hypoxia-inducible factor-1α-immunohistochemistry. (2010)
  • Author(s): Ueda M, et al.
  • Organizer: 2010 Society of Nuclear Medicine Annual Meeting.
  • Place of Presentation: Salt Lake City, USA.
  • Year and Date: 2010-06-06
• [Presentation] Tumor pretargeting in mice using an oxygen-dependent degradable streptavidin and a radioiodinated biotin : comparison between autoradiography and hypoxia-inducible factor-1α-immunohistochemistry (2010)
  • Author(s): Ueda M, Kudo T, Kuge Y, Mukai T, Miyano A, Ono M, Kizaka-Kondoh S, Hiraoka M, Saji H
  • Organizer: 2010 Society of Nuclear Medicine Annual Meeting
  • Place of Presentation: Salt Lake City, USA.
  • Year and Date: 2010-06-06
• [Presentation] 腫瘍内HIF-1存在領域のイメージング剤の開発:チミジンキナーゼ融合酸素依存的分解プローブに関する検討 (2009)
  • Author(s): 宮野梓、上田真史, 他
  • Organizer: 第49回日本核医学学術総会
  • Place of Presentation: 旭川
  • Year and Date: 2009-10-01
• [Presentation] 腫瘍内HIF-1存在領域のイメージング剤の開発:チミジンキナーゼ融合酸素依存的分解プローブに関する検討 (2009)
  • Author(s): 宮野梓、上田真史, 他
  • Organizer: 第49回日本核医学学術総会
  • Place of Presentation: 旭川市民文化会館(北海道)
  • Year and Date: 2009-10-01
• [Remarks] ホームページ等
  • URL: http://www.pharm.kyoto-u.ac.jp/byotai/
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/byotai/