{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:07:15Z","timestamp":1780387635610,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Esophageal squamous cell carcinoma (ESCC) often presents as flat lesions difficult to detect with conventional endoscopy, leading to poor prognosis. To overcome this, we developed a near\u2010infrared (NIR) molecular imaging strategy using an epidermal growth factor receptor (EGFR)\u2010targeted antibody and established a novel orthotopic microminipig (MMP) model for translational evaluation. First, cetuximab was labeled with Alexa Fluor 680 (AF680) and validated in\u00a0vitro for specific binding. Among five ESCC cell lines profiled for proliferation and antigen density, KYSE410 was selected for in\u00a0vivo studies due to its optimal balance of these factors. In mouse xenografts, AF680\u2010cetuximab tumor fluorescence peaked at 96\u2009h, achieving high signal\u2010to\u2010noise ratios. Subsequently, to establish a clinically relevant large\u2010animal platform, we optimized an immunosuppression protocol for MMPs. Through iterative testing, we determined that a combination of neonatal thymectomy and pharmacologic immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone), supplemented with antibiotics and proton\u2010pump inhibitors, was essential to prevent rejection, sepsis, and gastric ulcers. This optimized regimen enabled stable orthotopic engraftment of human ESCC via endoscopic submucosal injection in the MMP esophagus. Using a custom\u2010developed NIR fluorescence endoscope mimicking a clinical setting, we successfully visualized orthotopic tumors with clear margins at 96\u2009h post\u2010injection, subsequently confirmed by immunohistochemistry. In conclusion, AF680\u2010cetuximab enables specific, high\u2010contrast detection of ESCC. Furthermore, we report the first successful orthotopic engraftment of human cancer cells in immunosuppressed MMPs. This model provides a powerful platform for developing fluorescence\u2010guided endoscopic diagnostics and theranostics for early\u2010stage esophageal cancer, bridging the gap to future clinical application.<\/jats:p>","DOI":"10.1111\/cas.70378","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:55:31Z","timestamp":1775285731000},"page":"1678-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Orthotopic Esophageal Cancer Xenograft Model in Immunosuppressed Microminipigs for Near\u2010Infrared Fluorescence Endoscopy"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2715-5539","authenticated-orcid":false,"given":"Takanori","family":"Miyake","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima 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University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaroh","family":"Takagaki","sequence":"additional","affiliation":[{"name":"Bio\u2010Innovation Research Center Tokushima University  Tokushima Japan"},{"name":"Department of Anatomy and Systems Biology University of Yamanashi Faculty of Medicine  Yamanashi Japan"},{"name":"Section of Global Education Institute of Science Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaizo","family":"Kagemoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Kida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Oncology Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Sogabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and 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