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アイテム
Development of anti c-kit monoclonal antibody probe for SPECT imaging of gastrointestinal stromal tumor
https://repo.qst.go.jp/records/69526
https://repo.qst.go.jp/records/695267a6c5b46-8229-4bc4-b6a4-6e69426876c2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-10-21 | |||||
| タイトル | ||||||
| タイトル | Development of anti c-kit monoclonal antibody probe for SPECT imaging of gastrointestinal stromal tumor | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Sogawa, Chizuru
× Sogawa, Chizuru× Tsuji, Atsushi× Sugyou, Aya× Sudou, Hitomi× Okada, Keiichirou× Arano, Yasushi× Koizumi, Mitsuru× Furukawa, Takako× Harada, Yoshinobu× Saga, Tsuneo× 曽川 千鶴× 辻 厚至× 須尭 綾× 須藤 仁美× 岡田 圭一郎× 荒野 泰× 小泉 満× 古川 高子× 原田 良信× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Aim: Gastrointestinal stromal tumor (GIST) is a most common mesenchymal tumor arising from the human gastrointestinal tract. Overexpression of c-kit, encoding type III receptor tyrosine kinase, and its functional mutation is present in most GIST. 18F-fluoro-deoxyglucose (FDG) has been reported to highly accumulate in GISTs, and positron emission tomography using FDG (FDG-PET) is very useful for tumor detection and also for the assessment of early response to treatments using Imatinib (Gleevec). However, FDG-PET, in some cases, fails to detect relapse of GIST at early time point. If we could develop a specific method to detect c-kit expression, it can be used for the evaluation of the early response and relapse of GISTs. In this study, we labeled anti-c-kit antibodies with 125I and 111In, and assessed its in vitro and in vivo characteristics. Materials & methods: We constructed an expressing vector of mutated c-kit and transfected it to HEK293 human embryonic kidney cells and isolated several stable clones. To select highly expressing cell clones, we determined c-kit expression using western blot analysis and immunofluorescent staining. The cell suspension (1x107) was mixed with Matrigel, and injected subcutaneously in BALB/c-nu/nu male mice. We radiolabeled two anti-c-kit murine monoclonal antibodies (Mab1 and Mab2) with 125I using the chloramine-T or 3'-lodohippuryl-Ne-maleoyl-L-lysine (HML), and 111In using the 2-(p-isothiocyanatobenzyl) cyclohexyl-diethyl-enetriaminepentaacetic acid (CHX-A"-DTPA). We performed cell binding, competitive inhibition and internalization assays in vitro, and biodistribution and SPECT imaging in tumor-bearing mice. Results: We isolated 18 c-kit stably expressing cell clones, and determined 6 of them highly express c-kit using western blotting analysis. Immunofluorescent staining of c-kit highly expressing cells showed that c-kit is primarily localized on the cell membrane like the original GIST cell line, and developed tumors in mice. 125I-MAb1, 125I-MAb1(HML), 125I-Mab2, 111In-MAb1 and 111In-MAb2 specifically bound to c-kit expressing cells with affinity constants of 4.3x108M-1, 5.2x108M-1, 3.5x108M-1, 3.4x108M-1 and 3.9x108M-1, respectively. These antibodies were internalized, and 111In-labeled Mab1 highly accumulated in xenografted tumors, which were visualized by SPECT. Conclusion: These results showed that the radiolabeled c-kit antibody specifically accumulated in xenografted tumors and would be useful for the PET/SPECT imaging of GIST. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Annual Congress of the European Association of Nuclear Medicine 2008 | |||||
| 発表年月日 | ||||||
| 日付 | 2008-10-15 | |||||
| 日付タイプ | Issued | |||||
