@article{oai:repo.qst.go.jp:00047406, author = {D., McMillan Dayton and Maeda, Junko and Justin, Bell and D., Genet Matthew and Phoonswadi, Garrett and A., Mann Kelly and L., Kraft Susan and Kitamura, Hisashi and Fujimori, Akira and Yoshii, Yukie and Furukawa, Takako and Fujibayashi, Yasuhisa and Kato, Takamitsu and Justin Bell and 北村 尚 and 藤森 亮 and 吉井 幸恵 and 古川 高子 and 藤林 康久 and 加藤 宝光}, issue = {5}, journal = {Journal of Radiation Research}, month = {Aug}, note = {Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors.}, pages = {784--791}, title = {Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission}, volume = {56}, year = {2015} }