@misc{oai:repo.qst.go.jp:00065683,
 author = {Yoshii, Yukie and Furukawa, Takako and Matsumoto, Hiroki and Yoshimoto, Mitsuyoshi and Zhang, Ming-Rong and Kiyono, Yasushi and Fujibayashi, Yasuhisa and Saga, Tsuneo and 吉井 幸恵 and 古川 高子 and 松本 博樹 and 吉本 光喜 and 張 明栄 and 藤林 康久 and 佐賀 恒夫},
 month = {Jun},
 note = {64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a promising theranostic agent targeting over-reduced condition under hypoxia in tumors. Clinical studies on diagnosis with radiolabeled Cu-ATSM are currently conducted worldwide, revealing its prognostic value. However, detailed characteristics of the region of high 64Cu-ATSM uptake remained unclear. Here, using human colon carcinoma HT-29 model, we investigated characteristics of 64Cu-ATSM uptake regions relating to tumor malignancy, such as up-regulation of DNA repair and concentration of CD133+ cancer stem cells, and developed a strategy to enhance 64Cu-ATSM internal radiotherapy efficacy by inhibiting DNA repair with co-administration of nucleic acid (NA) antagonists. Methods: Distribution of 64Cu-ATSM was examined in HT29 tumors, and the samples from regions identified as 64Cu-ATSM high- and low-uptake regions were used for characterization. Gene expression profile, NA incorporation (BrdU uptake), and CD133+ cell ratio were studied. For in vivo treatment study, 64Cu-ATSM (37 MBq) injection with or without co-administration of NA antagonists was tested and compared to 64Cu-ATSM alone (37 or 74 MBq). Results: Up-regulation of the pathways related to DNA repair along with BrdU uptake, and elevated CD133+ cell ratio were observed in 64Cu-ATSM high-uptake regions. In treatment study, 64Cu-ATSM showed dose-dependent inhibition of tumor growth, although 74 MBq showed significant toxicity. Co-administration of NA antagonists with 37 MBq 64Cu-ATSM showed greater tumor growth suppression than 74 MBq 64Cu-ATSM alone, without significant toxicity, and effectively reduced CD133+ cell ratio. Conclusions: 64Cu-ATSM accumulation was associated with tumor malignant characteristics and 64Cu-ATSM therapy with NA antagonists could be an effective approach to target these characteristics., The Society of Nuclear Medicine (SNM) annual meeting 2015},
 title = {64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics},
 year = {2015}
}