Optical Metabolic Imaging to Characterize Early Treatment Response in Head and Neck Cancer

Abstract

Optimized therapies and methods to resolve treatment response could improve quality of life and survival for head and neck cancer patients. Optical metabolic imaging presents an advantageous method to address these needs by measuring intrinsic fluorescence from the metabolic cofactors NAD(P)H and FAD and calculating the optical redox ratio and fluorescence lifetimes of NAD(P)H and FAD. These parameters probe global cell metabolism as well as molecular protein-binding in metabolic signaling pathways. This dissertation work measures treatment response (p<0.05) by applying optical metabolic imaging to head and neck cancer in vitro and in vivo within 2 days of treatment with targeted therapies, chemotherapy, and drug combination. These measurements are characterized in established cell lines, head and neck cancer xenografts, human patient tissue, and three-dimensional organoid cultures. Gold standard measures validate treatment response, including cell proliferation, cell death, and tumor growth over 2 weeks of treatment. Additionally, high-resolution optical metabolic images qualitatively and quantitatively characterize cellular heterogeneity, which can impact patient response or resistance to treatment. Clinically, optical metabolic imaging could measure early response to treatment in head and neck cancer patients, thereby enabling intervention and reduced toxicities from ineffective therapies. Additionally, optical metabolic imaging could provide a platform to streamline drug discovery for head and neck cancer and predict personalized treatment regimens for patients.