EGFR-targeted dual-modal imaging for guiding resection and photoimmunotherapy in a pre-clinical head and neck cancer model

Surgical resection is a primary treatment for early-stage and locally advanced head and neck cancers, but intraoperative margin assessment remains challenging. Fluorescence imaging is widely used for tumor delineation but offers limited depth resolution and may miss microscopic disease. To address this, we developed a cetuximab-based antibody conjugate incorporating verteporfin (a photosensitizer) and a naphthalocyanine-derived photoacoustic contrast agent. In an orthotopic xenograft model, photoacoustic imaging enabled high-fidelity detection of tongue tumors, while verteporfin fluorescence precisely identified tumor margins. Complete resections guided by fluorescence imaging extended tumor-free survival. Additionally, in a partial resection model, photoimmunotherapy enhanced treatment outcomes. These results support the utility of this antibody conjugate for image-guided surgery and treatment of residual disease in head and neck cancer.