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Background <p>Gastrointestinal stromal tumors (GISTs) are malignant subepithelial tumors, known for their poor prognosis due to distant metastasis. Because GIST is covered by a normal mucosal layer, effective tissue biopsy under conventional endoscopy is difficult, thereby leading to delayed diagnosis and a dismal prognosis. We performed molecular imaging of GIST targeting c-KIT using fluorescence-labeled anti-c-KIT antibody/fragments and fluorescent endoscopy.</p> Methods <p>Mouse anti-human c-KIT monoclonal antibody, its F(ab′)<sub>2</sub> and Fab fragments were labeled with AF680. Two GIST cell lines (GIST-T1, GIST-882M) were used for experiments. Antibodies were intravenously administered to mice xenografted with GIST-T1 or GIST-882M, and each tumor was observed using IVIS Spectrum and self-developed simple fluorescent endoscopy.</p> Results <p>The GIST-T1 cell live imaging revealed strong signals on cell membranes after 1&#xa0;min incubation, and thereafter, they aggregated and internalized inside the cells within 130&#xa0;min in all antibody/fragment groups. In vivo mouse experiments, AF680-labeled IgG slowly accumulated in tumors peaking at 24&#xa0;h after injection. However, AF680-labeled F(ab′)<sub>2</sub> and Fab rapidly accumulated in tumors peaking at 1–2&#xa0;h, and completely cleared from the body within 24&#xa0;h. Fab showed the strongest fluorescence intensity in tumors. Fluorescence endoscopy could clearly detect GIST xenograft tumors 1–2&#xa0;h after AF680-labeled F(ab′)<sub>2</sub> and Fab injection.</p> Conclusions <p>AF680-labeled antibody/fragments showed clear and specific fluorescence signals in GIST xenografts in mice. Particularly, AF680-labeled Fab showed the strongest signal intensity at 1–2&#xa0;h post-administration and rapid clearance, suggestive of the safety. This approach may enable molecular imaging diagnosis of GIST by endoscopy in outpatient settings in the future.</p>

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Molecular imaging of gastrointestinal stromal tumor using anti-c-KIT antibody and its fragments

  • 期刊论文

  • 发表日期：

    2025年5月28日

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  • Takanori Kashihara,
  • Yutaka Kawano,
  • Shota Fujimoto,
  • Tatsuya Segawa,
  • Mamoru Shimizu,
  • Takanori Miyake,
  • Koichi Okamoto,
  • Naoki Muguruma,
  • Yasushi Sato,
  • Tetsuji Takayama

摘要

Background

Gastrointestinal stromal tumors (GISTs) are malignant subepithelial tumors, known for their poor prognosis due to distant metastasis. Because GIST is covered by a normal mucosal layer, effective tissue biopsy under conventional endoscopy is difficult, thereby leading to delayed diagnosis and a dismal prognosis. We performed molecular imaging of GIST targeting c-KIT using fluorescence-labeled anti-c-KIT antibody/fragments and fluorescent endoscopy.

Methods

Mouse anti-human c-KIT monoclonal antibody, its F(ab′)2 and Fab fragments were labeled with AF680. Two GIST cell lines (GIST-T1, GIST-882M) were used for experiments. Antibodies were intravenously administered to mice xenografted with GIST-T1 or GIST-882M, and each tumor was observed using IVIS Spectrum and self-developed simple fluorescent endoscopy.

Results

The GIST-T1 cell live imaging revealed strong signals on cell membranes after 1 min incubation, and thereafter, they aggregated and internalized inside the cells within 130 min in all antibody/fragment groups. In vivo mouse experiments, AF680-labeled IgG slowly accumulated in tumors peaking at 24 h after injection. However, AF680-labeled F(ab′)2 and Fab rapidly accumulated in tumors peaking at 1–2 h, and completely cleared from the body within 24 h. Fab showed the strongest fluorescence intensity in tumors. Fluorescence endoscopy could clearly detect GIST xenograft tumors 1–2 h after AF680-labeled F(ab′)2 and Fab injection.

Conclusions

AF680-labeled antibody/fragments showed clear and specific fluorescence signals in GIST xenografts in mice. Particularly, AF680-labeled Fab showed the strongest signal intensity at 1–2 h post-administration and rapid clearance, suggestive of the safety. This approach may enable molecular imaging diagnosis of GIST by endoscopy in outpatient settings in the future.