C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model

Nucl Med Biol. 2010 Feb;37(2):179-87. doi: 10.1016/j.nucmedbio.2009.10.008. Epub 2009 Nov 26.


Introduction: Gastrointestinal stromal tumor (GIST) is the most common 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 = 2.2-7.1x10(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 time, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacokinetics
  • Binding, Competitive
  • Biological Transport
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gastrointestinal Stromal Tumors / diagnostic imaging
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / metabolism*
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Indium Radioisotopes / chemistry*
  • Iodine Radioisotopes / chemistry
  • Male
  • Mice
  • Molecular Imaging / methods*
  • Mutation
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / immunology*
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Tomography, Emission-Computed, Single-Photon


  • Antibodies, Monoclonal
  • Indium Radioisotopes
  • Iodine Radioisotopes
  • Proto-Oncogene Proteins c-kit