OBJECTIVE: Combining the therapeutic and diagnostic properties of targeted antibodies may improve clinical assessment of disease with limited added toxicity during treatment. METHODS: Mice (n = 10) were xenografted with SCC-1 tumor cells and then treated with radiation, cisplatin and cetuximab. Brightfield and fluorescent imaging was performed after systemically injecting fluorescently labeled cetuximab prior to treatment and at six or ten weeks after initiation of treatment. The relative fluorescence intensity was determined for each image. RESULTS: The tumor luminosity measured before (week 0), during (week 6) and after treatment (week 10) did not significantly change. Actual tumor measurement corresponded to fluorescent measurements of tumors both before treatment and after treatment. Complete response to therapy occurred in one animal, where resolution of the tumor correlated with loss of fluorescent activity. CONCLUSIONS: This preclinical data suggests combining the diagnostic and therapeutic properties of cetuximab may be clinically useful.