@misc{oai:repo.qst.go.jp:00065050,
 author = {Yoshii, Yukie and Matsumoto, Hiroki and Yoshimoto, Mitsuyoshi and Furukawa, Takako and Morokoshi, Yukie and Sogawa, Chizuru and Zhang, Ming-Rong and Wakizaka, Hidekatsu and Fujibayashi, Yasuhisa and Saga, Tsuneo and 吉井 幸恵 and 松本 博樹 and 吉本 光喜 and 古川 高子 and 諸越 幸恵 and 曽川 千鶴 and 張 明栄 and 脇坂 秀克 and 藤林 康久 and 佐賀 恒夫},
 month = {Jun},
 note = {64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a promising internal radiotherapy (IRT) agent targeting tumor hypoxia. However, for clinical application of 64Cu-ATSM IRT, reduction of radiation to dose-limiting organs such as liver and intestines is critical. Here we developed a method to reduce radiation doses to normal organs while preserving tumor radiation dose by controlled administration of penicillamine, a copper chelator, in 64Cu-ATSM IRT. Methods: To examine effects of penicillamine, in vivo biodistribution studies were performed with HT-29 tumor-bearing mice with/without penicillamine administration. First, optimal injection interval of 64Cu-ATSM and penicillamine was tested. Optimal injection doses of penicillamine were then determined among single-dose administration of 100, 300 and 500 mg/kg at 1 h after 64Cu-ATSM injection or fractionated administration (100 mg/kg x 3) started at 1 h after 64Cu-ATSM injection with 1- or 2-h intervals. PET study and dosimetry analysis were also performed. Results: Penicillamine administration decreased 64Cu retention in liver and small intestine. Tumor uptake was not affected by penicillamine administration at 1 h after 64Cu-ATSM injection, but administration at 10 min before and after 64Cu-ATSM injection reduced tumor uptake. For single-dose injection, 300 mg/kg was optimal. Fractionated administration showed almost similar effect to single-dose injection, while inducing further prolonged decrease of liver retention. PET study showed same results as biodistribution study. Dosimetry analysis demonstrated controlled penicillamine administration enables to suppress radiation doses to critical organs below the tolerance levels in 64Cu-ATSM IRT. Conclusion: Controlled administration of penicillamine can reduce radiation exposure to normal organs in 64Cu-ATSM IRT, suggesting this method could be useful in clinical settings., SNMMI 2013 Annual Meeting},
 title = {Controlled administration of penicillamine reduces radiation exposure to normal organs in 64Cu-ATSM internal radiotherapy},
 year = {2013}
}