c-Met-targeted NIR-II imaging for precision management of oral squamous cell carcinoma and premalignant lesions.

Background: Poor outcomes in oral squamous cell carcinoma (OSCC) are closely linked to delayed diagnosis, positive surgical margins and occult lymph node metastasis. A unified strategy for premalignant lesion screening, primary tumor delineation and metastatic lymph node detection remains lacking. Methods: We evaluated c-Met expression in human oral lesions, OSCC tissues and metastatic lymph nodes to establish its suitability as an imaging target. On this basis, we developed IR788-Crizotinib, a c-Met-targeted near-infrared window-II (NIR-II) fluorescent probe, and evaluated its imaging performance in subcutaneous xenograft, 4-NQO-induced oral lesion, orthotopic tongue OSCC and lymph node metastasis mouse models. Results: c-Met expression increased progressively during oral lesion progression and remained high in metastatic tumor deposits within lymph nodes. IR788-Crizotinib identified high-risk lesions with 100% sensitivity and 96.77% accuracy, including severe dysplasia lesions as small as 300 μm and microinvasive OSCC lesions as small as 286 μm. In fluorescence-guided surgery models, the probe identified multifocal tumors and detected residual foci as small as 1 mm. In cervical lymph nodes, it detected micro-metastatic foci as small as 342 μm, with 100% sensitivity. Conclusions: c-Met-targeted NIR-II imaging provides an integrated visualization strategy for premalignant lesion screening, primary tumor delineation and metastatic lymph node detection in OSCC, with translational potential for precision management of oral cancer.