High-resolution simultaneous mapping of mitochondrial redox state and glucose uptake in human breast tumor xenografts.

Abstract

Tumor stratification on the basis of metabolic phenotypes may provide useful information for cancer diagnosis and treatment. Higher than normal glucose uptake/metabolism by cancer cells is an established hallmark for cancer staging by fluorinated deoxyglucose positron emission tomography (FDG-PET). High-resolution (down to 50 × 50 × 20 μm3) biomarkers of mitochondrial redox state provided by the redox scanning or the low-temperature 3-D NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins including FAD, i.e., flavin adenine dinucleotide) fluorescence imaging can differentiate human melanoma and breast cancer mouse xenografts of different metastatic potentials. In this project, by injecting into breast tumor bearing mice a near-infrared fluorescent glucose-analogue Pyro-2DG (pyropheophorbide 2-deoxyglucosamide), we were able to simultaneously image both the redox state and glucose uptake by mouse xenografts of human breast cancer MDA-MB-231 with an in-plane resolution of 200 μm. The preliminary results showed heterogeneity in the distribution of both Pyro-2DG uptake and the mitochondrial redox state, with Pyro-2DG uptake tending to correlate more with NADH distribution in tumor rim and also exhibiting pronounced uptake in localized areas of the tumor core. The co-registered images of mitochondrial redox state and glucose uptake may provide relevant information for understanding tumor metabolism and its role in cancer progression.