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Evaluation of a Novel Human Anti-EGFR Monoclonal Antibody as an Imaging Probe.
https://repo.qst.go.jp/records/63988
https://repo.qst.go.jp/records/63988d7100ddd-b4f5-4796-9fc8-bcd754f78d33
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-09-13 | |||||
| タイトル | ||||||
| タイトル | Evaluation of a Novel Human Anti-EGFR Monoclonal Antibody as an Imaging Probe. | |||||
| 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× Furukawa, Takako× Koizumi, Mitsuru× Kurosawa, Yoshikazu× Saga, Tsuneo× et.al× 曽川 千鶴× 辻 厚至× 古川 高子× 小泉 満× 黒澤 良和× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The epithelial growth factor receptor (EGFR) is over-expressed in many epithelial cancers, and is an attractive target for cancer imaging and therapy. Here we report a novel anti-EGFR human monoclonal antibody which was isolated from a human phage-display antibody library by comprehensive screening using living cancer cells. In this study, we selected one antibody from nine anti-EGFR antibody clones by cell binding assay and further assessed the selected antibody in vitro and in vivo regarding the potential as an imaging probe. Material and Methods: Nine anti-EGFR antibodies and cetuximab, a well-defined anti-EGFR antibody, were radiolabeled with 125I using chloramine-T method. Cell binding assay using human epidermal cancer cell line A431 highly expressing EGFR was performed to select an antibody showing the highest binding. The selected antibody was further radiolabeled with 111In by conjugating antibody with a bifunctional chelate, N-[(R)-2-Amino-3-(p-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A"-DTPA), and assessed by in vitro cell binding, competitive inhibition and internalization assays. The xenografted tumor was made by subcutaneous inoculation of 2x106 A431 cells into BALB/c-nu/nu mice, and in vivo biodistribution study, planar imaging and SPECT were performed after intravenous administration of 111In-labeled selected antibody. Results: The monoclonal antibody (048-006) was selected showing the highest binding to A431 cells among seven antibodies tested. 125I- and 111In-labeled 048-006 showed almost equivalent affinity constant to 125I- and 111In-labeled cetuximab (3.8x109M-1 and 1.8x109M-1 for 048-006 vs. 3.3x109M-1 and 2.3x109M-1 for cetuximab, respectively), and both antibodies were internalized after binding. 111In-048-006 showed high uptake in A431 tumors (highest tumor uptake of 15.98+/-3.65 %ID/gram obtained at 48 hours after injection), and the xenografted tumor was clearly visualized by planar and SPECT using 111In-048-006. Conclusion: Radiolabeled human anti-EGFR monoclonal antibody 048-006 would be promising for the imaging tumors with EGFR over-expression. |
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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 | World Molecular Imaging Congress 2010 | |||||
| 発表年月日 | ||||||
| 日付 | 2010-09-11 | |||||
| 日付タイプ | Issued | |||||
