@article{oai:repo.qst.go.jp:00046518,
 author = {Yoshida, Chisato and Tsuji, Atsushi and Sudou, Hitomi and Sugyou, Aya and Kikuchi, Tatsuya and Koizumi, Mitsuru and Arano, Yasushi and Saga, Tsuneo and 吉田 千里 and 辻 厚至 and 須藤 仁美 and 須尭 綾 and 菊池 達矢 and 小泉 満 and 荒野 泰 and 佐賀 恒夫},
 issue = {3},
 journal = {PLoS ONE (Online only:URL:http://www.plosone.org)},
 month = {Mar},
 note = {Abstract
Small cell lung cancer (SCLC) is an aggressive tumor and prognosis remains poor. Therefore, the development of more
effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8) accumulated in SCLC
xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2) for radioimmunotherapy (RIT)
of an SCLC mouse model by labeling with the 90Y isotope.
Methods: 111In- or 125I-labeled antibodies were evaluated in vitro by cell binding, competitive inhibition and cellular
internalization assays in c-kit-expressing SY cells and in vivo by biodistribution in SY-bearing mice. Therapeutic efficacy of
90Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7.
Results: [111In]12A8 and [111In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively). 67A2 was
internalized similar to 12A8. High levels of [111In]12A8 and [111In]67A2 accumulated in tumors, but not in major organs.
[111In]67A2 uptake by the tumor was 1.7 times higher than for [111In]12A8. [90Y]12A8, but not [90Y]67A2, suppressed tumor
growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [90Y]12A8, and 1.85 and 3.7 MBq of [90Y]67A2
(absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively) almost completely disappeared approximately 2 weeks after
injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [90Y]67A2. The area of necrosis
and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [90Y]12A8,
whereas no dose-dependent increase was observed following [90Y]67A2 treatment. Body weight was temporarily reduced
but all mice tolerated the RIT experiments well.
Conclusion: Treatment with [90Y]12A8 and [90Y]67A2 achieved a complete therapeutic response when SY tumors received
an absorbed dose greater than 18 Gy and thus are promising RIT agents for metastatic SCLC cells at distant sites.},
 title = {Therapeutic Efficacy of C-Kit-Targeted Radioimmunotherapy Using 90Y-Labeled Anti-C-Kit Antibodies in a Mouse Model of Small Cell Lung Cancer},
 volume = {8},
 year = {2013}
}