ArticleEsophagus : official journal of the Japan Esophageal Society2026
A GLUT1-targeted peptide tracer for precision molecular imaging of esophageal squamous cell carcinoma: from early detection to intraoperative margin assessment.
Article in Esophagus : official journal of the Japan Esophageal Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is characterized by poor prognosis due to the low sensitivity of early endoscopic detection and the difficulty in delineating narrow surgical margins intraoperatively. Glucose transporter 1 (GLUT1) is a key metabolic biomarker in ESCC, but no ESCC-specific near-infrared (NIR) fluorescent tracer has been developed to exploit this target for clinical imaging applications.
methodsGLUT1 expression was systematically evaluated in 31 formalin-fixed paraffin-embedded ESCC tissues (6 intramucosal/early-stage, 25 advanced-stage) and paired adjacent normal tissues using immunohistochemistry. A GLUT1-targeting peptide (G12) was identified via solid-phase phage display technology and conjugated to the NIR fluorophore Cy7 to construct the tracer G12-Cy7. The specificity of G12-Cy7 was validated in KYSE-30 ESCC cells using immunofluorescence blocking assays and flow cytometry. In vivo targeting efficacy and pharmacokinetics were assessed in KYSE-30 xenograft models using an IVIS Spectrum imaging system.
resultsGLUT1 was highly and specifically expressed in 96% of advanced ESCC tissues and all intramucosal lesions, with minimal expression in adjacent normal esophageal mucosa (advanced ESCC vs. normal mucosa, p = 0.000023; intramucosal ESCC vs. normal mucosa, p = 0.0089). The synthesized G12-Cy7 tracer exhibited high purity and structural integrity. In vitro, G12-Cy7 bound specifically to GLUT1-positive ESCC cells, and this binding was abrogated by GLUT1 antibody pre-blocking. In vivo, G12-Cy7 specifically accumulated in ESCC xenografts, achieving a tumor-to-background ratio (TBR) of ~ 1.5, which is sufficient for distinguishing small mucosal lesions and defining surgical margins in the esophageal context.
conclusionGLUT1 is a reliable imaging target expressed across both early and advanced stages of ESCC. The novel peptide-based tracer G12-Cy7 demonstrates high specificity and favorable in vivo imaging characteristics, making it a promising preclinical molecular tool that lays the foundation for addressing the critical clinical unmet needs of early ESCC detection and precise intraoperative margin assessment.
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