Optical Imaging Approaches to Investigating Radiation Resistance

Abstract

Radiation therapy is frequently the first line of treatment for over 50% of cancer patients. While great advances have been made in improving treatment response rates and reducing damage to normal tissue, radiation resistance remains a persistent clinical problem. While hypoxia or a lack of tumor oxygenation has long been considered a key factor in causing treatment failure, recent evidence points to metabolic reprogramming under well-oxygenated conditions as a potential route to promoting radiation resistance. In this review, we present recent studies from our lab and others that use high-resolution optical imaging as well as clinical translational optical spectroscopy to shine light on the biological basis of radiation resistance. Two-photon microscopy of endogenous cellular metabolism has identified key changes in both mitochondrial structure and function that are specific to radiation-resistant cells and help promote cell survival in response to radiation. Optical spectroscopic approaches, such as diffuse reflectance and Raman spectroscopy have demonstrated functional and molecular differences between radiation-resistant and sensitive tumors in response to radiation. These studies have uncovered key changes in metabolic pathways and present a viable route to clinical translation of optical technologies to determine radiation resistance at a very early stage in the clinic.

Cherenkov light emission in external beam radiation therapy of the larynx

“…In this context, monitoring tumour metabolism and hemodynamics plays an important role, as these are early indicators of treatment efficacy and predictors for tumour response to treatment [8]. Optical imaging has unique potential for this purpose, whilst being non-ionising and cost effective [9][10][11][12][13][14][15][16].…”