In Vivo Metabolic Evaluation of Breast Tumor Mouse Xenografts for Predicting Aggressiveness Using the Hyperpolarized 13C-NMR Technique

Abstract

In vivo imaging/spectroscopic biomarkers for solid tumor aggressiveness are needed in the clinic to facilitate cancer diagnosis and treatment strategies. In mouse models of human melanoma and breast cancer, we were able to detect the metabolic differences among tumors of different metastatic potential and between normal and cancer tissues by optical imaging of the mitochondrial redox state of snap-frozen tissue samples. Such metabolic differences indicate that tumors of different aggressiveness have different metabolic homeostasis, which supports that kinetic parameters such as rate constant(s) can also serve as biomarkers for cancer aggressiveness and treatment response. Here we present our preliminary study on the mouse xenografts of the aggressive and indolent human breast cancer cell lines using the hyperpolarized (13)C-NMR (HP-NMR) technique. By recording the time courses of (13)C-pyruvate tracer and its metabolite signals in vivo, particularly the (13)C-lactate signal, the apparent rate constants of both the forward and reverse reactions catalyzed by lactate dehydrogenase (LDH) were extracted via the ratiometric modeling of the two-site exchange reaction that we developed. Data from four breast tumors (MCF-7, MDA-MB-468, and MDA-MB-231 medium and large) with different aggressiveness are included. We demonstrate the feasibility to quantify the apparent rate constants of LDH reactions in breast tumor xenografts.