Development of novel hypoxia imaging probes with a novel retention mechanism and high versatility

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15468
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Umeda Izumi, O. 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (40160791)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Hideyo 帝京大学, 薬学部, 教授 (10266348) ; NAKAMURA Takeshi 国立がん研究センター, 先端医療開発センター・機能診断開発分野, 特任研究員 (10624611)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 低酸素 / イメージング / がん / SPECT / Tc-99m

Outline of Final Research Achievements

Hypoxia is a characteristic feature of most solid tumors and closely related to tumor malignancy and treatment-resistance; therefore, in vivo visualization of tumor hypoxia promises to greatly contribute for optimization of cancer therapy. We herein developed new SPECT probes with a unique retention mechanism, differing from conventional nitroimidazole derivatives. In cell-based assay, our Tc-99m-labeled probes demonstrated significantly higher uptake in hypoxic cells than in normoxic cells, indicating the validity of our strategy. Animal studies revealed that their tissue distribution pattern including tumor accumulation were greatly different depending on the structure of ligand components. By modifying them, they successfully accumulated in the hypoxic region in the tumor. In vivo SPECT/CT images clearly depicted their uptake in tumors. Tc-99m is the most common nuclide for nuclear medicine probes, therefore they are quite promising as general clinical probes for hypoxia imaging.

Free Research Field

分子イメ－ジング、放射性薬品化学、腫瘍核医学