Hepatic gluconeogenesis influences ¹³C enrichment in lactate in human brain tumors during metabolism of [1,2-¹³C]acetate

¹³C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and ¹³C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed ¹³C-¹³C spin-spin coupling in ¹³C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-¹³C]acetate prior to the surgery. We found, in four patients, that infusion of ¹³C-enriched acetate was associated with synthesis of ¹³C-enriched glucose, detectable in plasma. ¹³C labeled glucose derived from [1,2-¹³C]acetate metabolism in the liver and the brain pyruvate recycling in the tumor together lead to the production of the ¹³C labeled lactate pool in the brain tumor. Their combined contribution to acetate metabolism in the brain tumors was less than 4.0%, significantly lower than the direct oxidation of acetate in the citric acid cycle in tumors.