Evaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma.
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<b>Background:</b> 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. <b>Methods:</b> Functional MRI and <sup>18</sup>F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CAL<sup>R</sup>) and sensitive (CAL<sup>S</sup>) HNSCC xenografts <i>in vivo</i>, and pathological correlates sought. <b>Results:</b> Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baseline R2∗ , lower hyperoxia-induced ΔR2∗ and volume transfer constant K<sup>trans</sup> in the CAL<sup>R</sup> tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR<sub>1</sub> or water diffusivity between the CAL<sup>R</sup> and CAL<sup>S</sup> xenografts. PET revealed significantly higher relative uptake of <sup>18</sup>F-FDG in the CAL<sup>R</sup> cohort, which was associated with significantly greater Glut-1 expression. <b>Conclusions:</b> CAL<sup>R</sup> xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CAL<sup>S</sup> tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.
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Preclinical Molecular Imaging
Radiotherapy Physics Modelling
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Frontiers in oncology, 2018, 8 pp. 271 - ?