The negative impact of tumor hypoxia on radiotherapeutic efficacy is well recognized. However, an easy to use, reliable imaging method for assessment of tumor oxygenation in routine clinical practice remains elusive. Photoacoustic imaging (PAI) is a relatively new imaging technique that utilizes a combination of light and ultrasound (US) to enable functional imaging of tumor hemodynamic characteristics in vivo. Several clinical trials are currently evaluating the utility of PAI in cancer detection for breast, thyroid, and prostate cancer. Here, we evaluated the potential of PAI for rapid, label-free, non-invasive quantification of tumor oxygenation as a biomarker of radiation response in head and neck cancer. Methods: Studies were performed human papilloma virus- positive (HPV+) and -negative (HPV-) patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC). PAI was utilized for longitudinal assessment of tumor hemodynamics (oxygenation saturation and hemoglobin concentration) before, during and after fractionated radiation therapy (fRT). Imaging datasets were correlated with histologic measures of vascularity (CD31), DNA damage (phosphorylated γH2AX) and statistical modeling of tumor growth. Results: A differential response to fRT was observed between HPV+ and HPV- xenografts. Temporal changes in tumor hemodynamics (oxygen saturation and hemoglobin concentration) measured by PAI showed significant association with treatment outcomes. PAI-based changes in oxygen saturation were detected within days after initiation of fRT prior to detectable change in tumor volume, highlighting the potential of PAI to serve as an early biomarker of therapeutic efficacy. Consistent with PAI results, immunohistochemical staining of vascularity (CD31) and DNA damage (phosphorylated γH2AX) revealed distinct patterns of response in HPV+ and HPV- xenografts. Conclusion: Collectively, our observations demonstrate the utility of PAI for temporal mapping of tumor hemodynamics and the value of PAI read-outs as surrogate measures of radiation response in HNSCC.
Keywords: PDX; head and neck cancer; hypoxia; photoacoustic imaging; radiation.