Correlation of hyperpolarized 13 C-MRI data with tissue extract measurements.

Abstract

Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since -lactate signal levels obtained from HP imaging depend on multiple factors, such as the rate of substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA-MB-231 xenograft model in nude rats were used to test for correlations between the in vivo data and the ex vivo measures. The lactate-to-pyruvate ratio from HP MRI was strongly correlated with [1- ]lactate concentration measured from the extracts using NMR (R = 0.69, p 0.05), as well as negatively correlated with tumour wet weight (R = 0.60, p 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( = 0.78 and 0.93, respectively, p 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly correlated.