@article{oai:repo.qst.go.jp:00046232, author = {Yoshii, Yukie and Furukawa, Takako and Kiyono, Yasushi and Watanabe, Ryo and Waki, Atsuo and Mori, Tetsuya and Yoshii, Hiroshi and Oh, Myungmi and Asai, Tatsuya and Okazawa, Hidehiko and Fujibayashi, Yasuhisa and et.al and 吉井 幸恵 and 古川 高子 and 清野 泰}, issue = {4}, journal = {Nuclear Medicine and Biology}, month = {Feb}, note = {Introduction: 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a potential imaging agent of hypoxic tumor for use with PET. Recent literature indicates that cancer cells expressing CD133, which is a frequently used marker for so-called cancer stem cells or cancer stem cell-like cells (collectively referred here as CSC's), contribute to tumor's therapeutic resistance and metastasis ability and possess hypoxia resistance. Here, we investigated relationships between 64Cu- ATSM accumulation and existence of CD133+ cells using mouse colon carcinoma (Colon-26) tumor. Methods: Intratumor distribution of 64Cu-ATSM and 18F-fluorodeoxyglucose (18FDG) was compared with immunohistochemical staining for CD133 with a Colon-26 model. In addition, in vitro characterization of CD133+ Colon-26 cells was performed. Results: In Colon-26 tumors, 64Cu-ATSM localized preferentially in regions with a high density of CD133+ cells. The percentage of CD133+ cells was 11-fold higher in 64Cu-ATSM high uptake regions compared with 18FDG high (but 64Cu-ATSM low) uptake regions. CD133+ Colon-26 cells showed characteristics, which have been previously linked with CSC's in other cancer cell lines, such as high colony-forming ability, high tumor-initiating ability, and hypoxia resistance. In vitro culturing of Colon- 26 cells under hypoxia and/or glucose starvation showed that CD133+ cells were resistant to hypoxia and glucose starvation, and 64Cu-ATSM uptake was increased under such conditions. Conclusions: Our findings indicate that, in Colon-26 tumors, 64Cu-ATSM accumulates in CD133+ cell-rich regions and that CD133+ Colon-26 cells were highly tumorigenic and resistant to hypoxia and glucose starvation. Therefore 64Cu-ATSM could be a potential imaging agent for rich regions of CD133+ cells, associated with CSC's, within tumors.}, pages = {395--404}, title = {Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) accumulates in rich regions of CD133+highly tumorigenic cells in mouse colon carcinoma}, volume = {37}, year = {2010} }