論文

査読有り
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
  • Chizuru Sogawa
  • ,
  • Atsushi B. Tsuji
  • ,
  • Hitomi Sudo
  • ,
  • Aya Sugyo
  • ,
  • Chisato Yoshida
  • ,
  • Kenichi Odaka
  • ,
  • Tomoya Uehara
  • ,
  • Yasushi Arano
  • ,
  • Mitsuru Koizumi
  • ,
  • Tsuneo Saga

37
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.

リンク情報
DOI
https://doi.org/10.1016/j.nucmedbio.2009.10.008
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000274947300009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.nucmedbio.2009.10.008
  • ISSN : 0969-8051
  • Web of Science ID : WOS:000274947300009

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