@article{oai:repo.qst.go.jp:00046231, author = {Yoshii, Yukie and Furukawa, Takako and Kiyono, Yashushi and Mori, Tetsuya and Watanabe, Ryo and Yoshii, Hiroshi and Fujibayashi, Yasuhisa and et.al and 吉井 幸恵 and 古川 高子 and 藤林 康久}, issue = {2}, journal = {Nuclear Medicine and Biology}, month = {Oct}, note = {Introduction 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is an imaging agent for positron emission tomography (PET) that targets hypoxic tumors. 64Cu-ATSM is also reported to be a potential agent for internal radiotherapy. In a mouse colon carcinoma (Colon-26) model, we have shown that 64Cu-ATSM preferentially localizes in intratumoral regions with a high density of CD133+ cells, which show characteristics of cancer stem cells or cancer stem cell-like cells (collectively referred here as CSCs). In this study, we evaluated the therapeutic effect of 64Cu-ATSM in relation to CD133 expression using this model. \nMethods Systemic administration of 37 MBq 64Cu-ATSM or saline was conducted twice within a 1-week interval to mice bearing 1-week-old Colon-26 tumors (days 0–7). At day 19, tumor size measurement, flow cytometry analysis and experimental lung metastatic assay were performed. The therapeutic effect of 64Cu-ATSM on sorted CD133+ and CD133− Colon-26 cells was also examined in vitro. \nResults In vivo studies showed that 64Cu-ATSM treatment inhibited tumor growth. The percentage of CD133+ cells and metastatic ability in 64Cu-ATSM treated tumors was decreased compared with that in control animals. In vitro studies demonstrated that 64Cu-ATSM accumulated in cells under hypoxic conditions and incorporation of 64Cu-ATSM under hypoxia caused cell death in both CD133+ and CD133− cells in a similar extent. \nConclusions 64Cu-ATSM administration reduced tumor volume as well as the percentage of CD133+ cells and the metastatic ability of Colon-26 tumors. Together with our data, it is suggested that 64Cu-ATSM accumulates in regions high in CD133+ highly tumorigenic cells and kills such regions by radiation, resulting in a decrease of the percentage of CD133+ cells.}, pages = {151--157}, title = {Internal radiotherapy with copper-64-diacetyl-bis (N4-methylthiosemicarbazone) reduces CD133+ highly tumorigenic cells and metastatic ability of mouse colon carcinoma}, volume = {38}, year = {2010} }