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

NMR in Biomedicine
Casey Y LeeCharles H Cunningham

Abstract

Hyperpolarized (HP) 13 C MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since 13 C -lactate signal levels obtained from HP 13 C imaging depend on multiple factors, such as the rate of 13 C 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 13 C 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 13 C data and the ex vivo measures. The lactate-to-pyruvate ratio from HP 13 C MRI was strongly correlated with [1- 13 C ]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 ( ρ = 0.78 and 0.93, respectively, p < 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly ...Continue Reading

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