@misc{oai:repo.qst.go.jp:00071344, author = {Hasegawa, Sumitaka and Furukawa, Takako and Saga, Tsuneo and 長谷川 純崇 and 古川 高子 and 佐賀 恒夫}, month = {Oct}, note = {Radionuclide therapy kills tumor cells by the placement of unsealed therapeutic radionuclide in the tumor for the selective delivery of radiation to tumors. Enhanced delivery of therapeutic radionuclide, especially short-range particle emitters, to tumor cell nucleus may induce an increased numbers of lethal DNA damage and cell death, leading to more effective treatment of tumor. Here we report that we generated trastuzumab (Her) modified with nuclear localization signal (NLS) to enhance the delivery of therapeutic radioisotopes to cell nucleus of HER2-overexpressing tumors. A synthetic 13mer peptide including NLS-motif derived from SV40 large T-antigen was attached to Her, a HER2-targeting antibody, by chemical crosslinking. The nuclear localizing Her antibodies (Her-NLS) labeled with auger electron emitters such as iodine-125 were bound to HER2-overexpressing cancer cells and rapidly internalized in the cells. Her-NLS showed enhancement of nuclear localization compared with Her. Nuclear localizing trastuzumab will be useful for HER2-targeting radionuclide therapy using short-range particle emitters such as auger-electron emitters and alpha particle emitters., 第72回日本癌学会学術総会}, title = {Generation of nuclear localizing antibody for targeted radionuclide therapy}, year = {2013} }