@misc{oai:repo.qst.go.jp:00072884,
 author = {Yoshii, Yukie and Yoshimoto, Mitsuyoshi and Matsumoto, Hiroki and Furukawa, Takako and Zhang, Ming-Rong and Inubushi, Masayuki and Tsuji, Atsushi and Fujibayashi, Yasuhisa and Higashi, Tatsuya and Saga, Tsuneo and 吉井 幸恵 and 吉本 光喜 and 古川 高子 and 張 明栄 and 犬伏 正幸 and 辻 厚至 and 藤林 康久 and 東 達也 and 佐賀 恒夫},
 month = {May},
 note = {Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an antiangiogenic agent clinically used for various cancers. However, repeated use of this agent leads to tumor-decreased vascularity and hypoxia, which results in drug delivery deficiency and induction of malignant behaviors in tumors. To address this, we focused on a theranostic agent, 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), which possesses high tissue permeability and can target the over-reduced state under hypoxia within tumors. The efficacy of internal radiotherapy with 64Cu-ATSM was examined in mice bearing tumors with bevacizumab-induced vascular decrease and hypoxia. Methods: Human colon carcinoma HT-29 tumor-bearing mice were treated with bevacizumab (5 mg/kg twice a week) for 3 weeks to produce a model for tumors with bevacizumab-induced vascular decrease and hypoxia. Characteristics within the bevacizumab-treated tumors were examined. Dual-isotope simultaneous SPECT/PET/CT imaging with a blood pool-detecting agent 99mTc-labeled human serum albumin and 64Cu-ATSM was performed. In vivo treatment study was then performed. Results: The bevacizumab-treated HT-29 tumors showed decreased blood vessel density, activation of the HIF-1 signaling pathway and upregulation of genes involved in this pathway, and increased uptake of 64Cu-ATSM, compared to the control. SPECT/PET/CT imaging showed reduced vascularity and increased proportion of hypoxic areas in the bevacizumab-treated tumors. 64Cu-ATSM therapy was effective to inhibit tumor growth and prolong survival in the bevacizumab-treated tumor-bearing mice without major adverse effects. Conclusion: 64Cu-ATSM therapy effectively enhanced anti-tumor effects in tumors with bevacizumab-induced vascular decrease and hypoxia. 64Cu-ATSM therapy could be an additional treatment to antiangiogenic therapy., 第12回日本分子イメージング学会学術集会},
 title = {64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia: Imaging analysis with dual-isotope simultaneous SPECT/PET/CT},
 year = {2017}
}