Real-Time In-Vivo Metabolic Characterization in Spontaneous Hepatocellular Carcinoma Using a Novel Transgenic Mouse Model

Philip Lee¹, Emilie Bard², George Radda¹

By incorporating a human hepatitis-B transgene and inducing mutagenesis via a sleeping-beauty-transposon system, a sophisticated liver cancer model has been created to study human hepatocellular carcinoma in mice. To understand changes in metabolic fuel demand as the disease progresses, hyperpolarized carbon-13 technology was utilized to study pyruvate metabolism in-vivo. We observe a reduction in the oxidative decarboxylation of pyruvate, with slight increases in transamination to alanine and reduction to lactate. Biochemical assay of liver extracts suggests an elevated dependence on glutamine as an anaplerotic carbon source. Metabolic imaging of downstream products such as lactate and alanine provides a map of tumor energetics.