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Background:  Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop acquired resistance. Strategies to identify HNSCC patients likely to benefit from EGFR-targeted therapies, together with biomarkers of treatment response, would have clinical value.   Methods:  Functional MRI and  18 F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CAL R ) and sensitive (CAL S ) HNSCC xenografts  in vivo , and pathological correlates sought.   Results:  Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baselineR  2∗, lower hyperoxia-inducedΔ   R  2∗and volume transfer constant K trans  in the CAL R  tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR 1  or water diffusivity between the CAL R  and CAL S  xenografts. PET revealed significantly higher relative uptake of  18 F-FDG in the CAL R  cohort, which was associated with significantly greater Glut-1 expression.   Conclusions:  CAL R  xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CAL S  tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.

Evaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma