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.