@misc{oai:repo.qst.go.jp:00064266,
 author = {Yoshida, Chisato and Tsuji, Atsushi and Koizumi, Mitsuru and Arano, Yasushi and Saga, Tsuneo and 吉田 千里 and 辻 厚至 and 小泉 満 and 荒野 泰 and 佐賀 恒夫},
 month = {Dec},
 note = {C-kit is a tyrosine kinase-type receptor for the stem cell factor. C-kit is highly expressed in some cancers such as gastrointestinal stromal tumors and small cell lung cancer (SCLC), in which autocrine/paracrine mechanisms stimulate tumor growth. SCLC, representing about 20% of all lung cancer types, is an aggressive form of lung cancers and tends to develop metastases to lymph nodes and other organs at an early stage. Although SCLC is sensitive to chemotherapy and radiation, the overall prognosis remains poor, and the development of effective therapies is needed for SCLC patients. In this study, the potential of two anti-c-kit monoclonal antibodies (Mab1 and Mab2) for the radioimmunotherapy of SCLC was evaluated in mouse model. Methods: Mabs were conjugated with CHX-A-DTPA and were labeled with 111In and 90Y. Cell binding, competitive inhibition and internalization assays were performed using 111In-labeled Mabs and a human SCLC cell line, SY, highly expressing c-kit. Biodistribution study of 111In-labeled Mabs was performed using nude mice bearing SY tumors. Therapeutic efficacy was also estimated after injecting 90Y-labeled Mabs (0, 20, 50 or 100 Ci) to SY-bearing mice and subsequent measuring the tumor size of SY-bearing mice twice a week until day 30. Results: In vitro studies showed that 111In-labeled Mabs specifically bound to SY cells with high affinities and were quickly internalized into cells after binding to c-kit. Biodistribution studies showed that tumor uptake of 111In-labeled Mab1 and Mab2 at maximum were 23.3+/-2.3 and 31.5+/-7.7 %ID/g, respectively. Administration of 90Y-labeled Mabs was well tolerated by all mice. 90Y-labeled Mab1 and Mab2 showed dose-dependent therapeutic effect, in which the administration of 100 Ci of 90Y-labeled Mabs significantly suppressed tumor growth including complete disappearance of the tumor in most mice. Conclusion: These 90Y-labeled anti-c-kit Mabs have the potential for radioimmunotherapy of c-kit-expressing SCLC., The International Chemical Congress of Pacific Basin Societies　（2010 Pacifichem）},
 title = {C-kit Targeted Radioimmunotherapy of Small Cell Lung Cancer in Nude Mice using Anti-c-kit Antibodies},
 year = {2010}
}