Development of an Endoscopic Auto-Fluorescent Sensing Device to Aid in the Detection of Breast Cancer and Inform Photodynamic Therapy

Abstract

Breast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent biomarkers that lend insight into cell and tissue metabolism. As such, we developed an endoscopic device to measure these metabolites in tissue to differentiate between malignant tumors and normal tissue. We performed initial validations in liquid phantoms as well as compared to a previously validated redox imaging system. We also imaged ex vivo tissue samples after modulation with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and a combination of rotenone and antimycin A. We then imaged the rim and the core of MDA-MB-231 breast cancer tumors, with our results showing that the core of a cancerous lesion has a significantly higher optical redox ratio ([FAD]/([FAD] + [NADH])) than the rim, which agrees with previously published results. The mouse muscle tissues exhibited a significantly lower FAD, higher NADH, and lower redox ratio compared to the tumor core or rim. We also used the endoscope to measure NADH and FAD after photodynamic therapy treatment, a light-activated treatment methodology. Our results found that the NADH signal increases in the malignancy rim and core, while the core of cancers demonstrated a significant increase in the FAD signal.

Fluorescence microscopy imaging of mitochondrial metabolism in cancer cells

“…Overall, there is a growing interest in imaging mitochondrial metabolism and to validate metabolic imaging as a tool to follow carcinogenesis, evaluate tumor therapy and to distinguish between cancerous and healthy tissue (64). The capability of applying these techniques to intraoperative histopathology at subcellular resolution (65) may revolutionize cancer therapy in the future (66,67). Light microscopy in the different imaging modalities described here became an essential tool to study mitochondrial metabolism in cancer.…”