2010年2月
C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model
NUCLEAR MEDICINE AND BIOLOGY
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- 巻
- 37
- 号
- 2
- 開始ページ
- 179
- 終了ページ
- 187
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.nucmedbio.2009.10.008
- 出版者・発行元
- ELSEVIER SCIENCE INC
Introduction: Gastrointestinal stromal tumor (GIST) is the most common a mesenchymal tumor arising from the gastrointestinal tract and highly expresses mutated c-kit. We aimed to develop a specific and sensitive method for detecting GISTs using radiolabeled anti-c-kit monoclonal antibody.
Methods: A mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. (125)I- and (111)In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice.
Results: Both (125)I- and (111)In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2-7.1 x 10(9) M(-1)). Internalization assay showed that (125)I-labeled antibodies were rapidly internalized and dehalogenated, with the release of (125)I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, (111)In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of (125)I-labeled antibody was low on Day 1, further decreasing with titre, while tumor uptake of (111)In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of (111)In-labeled antibody.
Conclusion: The anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs. (C) 2010 Elsevier Inc. All rights reserved.
Methods: A mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. (125)I- and (111)In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice.
Results: Both (125)I- and (111)In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2-7.1 x 10(9) M(-1)). Internalization assay showed that (125)I-labeled antibodies were rapidly internalized and dehalogenated, with the release of (125)I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, (111)In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of (125)I-labeled antibody was low on Day 1, further decreasing with titre, while tumor uptake of (111)In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of (111)In-labeled antibody.
Conclusion: The anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs. (C) 2010 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.nucmedbio.2009.10.008
- ISSN : 0969-8051
- Web of Science ID : WOS:000274947300009