WE‐E‐BRE‐12: Tumor Microenvironment Dynamics Following Radiation

Abstract

Purpose:This work aims to understand the radiation‐induced interplay between tumor oxygenation and metabolic activity. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient‐specific adaptive radiotherapy.Methods:Using patient‐derived xenografts of head and neck cancer we assessed tumor oxygenation via fiber‐optic probe monitored hemoglobin saturation and Blood Oxygen Level Dependent (BOLD) MRI. Measurements were taken before and after a 10 Gy dose of radiation. Changes in metabolic activity were measured via Fluorescence Lifetime IMaging (FLIM) with the appropriate controls following a 10 Gy dose of radiation. FLIM can non‐invasively monitor changes in fluorescence in response to the microenvironment including being able to detect free and bound states of the intrinsically fluorescent metabolite NADH (Nicotinamide Adenine Dinucleotide). With this information FLIM can accurately quantify the metabolic state of cells that have been radiated. To model the observed changes, a two‐compartment, source‐sink simulation relating hemoglobin saturation and metabolic activity was performed using MATLAB.Results:Hemoglobin saturation as measured by interstitial probe and BOLD‐MRI decreased by 30% within 15 minutes following radiation. FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways. Simulation of radiation‐induced alterations in tumor oxygenation demonstrated that these changes can be the result of changes in either vasculature or metabolic activity.Conclusion:Radiation induces significant changes in hemoglobin saturation and metabolic activity. These alterations occur on time scales approximately the duration of common radiation treatments. Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response.