Cellular accumulation of Cu-ATSM and NADH/NAD+ ratio in cytosol

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09911
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Nagoya University (2016-2018); National Institute of Radiological Sciences (2015)
• Principal Investigator: Furukawa Takako 名古屋大学, 医学系研究科(保健), 教授 (00221557)
• Co-Investigator(Renkei-kenkyūsha): Jin Zhao-Hui 国立研究開発法人量子科学技術研究開発機構 量子医学・医療部門 放射線医学総合研究所, 分子イメージング診断治療研究部, 主任研究員 (70324150)
• Research Collaborator: Oguri Ryota ; Takekawa Koki ; Hiramatsu Wakahiko
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 放射性医薬品 / PET / 腫瘍 / 低酸素 / CuATSM / redox

Outline of Final Research Achievements

Cu-ATSM labeled with positron emitting radioisotopes is supposed to accumulate into hypoxic tissues and expected to play a critical role in detecting hypoxic cancer and help to predict prognosis and select therapy strategy. The relation between cancer hypoxia and Cu-ATSM accumulation is, however, still ambiguous, hindering the interpretation of Cu-ATSM accumulation and its utilization. In this study, we established cell lines stably expressing newly developed Peredox protein which can report cytoplasmic NADH/NAD+ ratio as green/red fluorescence ratio, and demonstrated that cellular accumulation of Cu-ATSM depends on the cytoplasmic NADH/NAD+ ratio which reflects the redox status of cancer cell cytoplasm and the presence of hypoxia.

Free Research Field

分子イメージング

Academic Significance and Societal Importance of the Research Achievements

細胞質のNADH/NAD+比をレポートする蛍光タンパク質、Peredox、を用いることで、がん細胞への64Cu-ATSM集積が、腫瘍の低酸素によって引き起こされる細胞質のNADH/NADH+比の上昇を反映していることを、生きたがん細胞において示すことが出来た。64Cu-ATSMの腫瘍細胞への集積機序と腫瘍低酸素との関係を明らかにすることで、64Cu-ATSM PETイメージングの予後予測、治療法選択における有用性の根拠となる一つの因子を提案することが出来た。