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

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.

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.

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.

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.