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Glucose and lactate are primary substrates in cerebral energy metabolism. Hyperpolarized 1-13Cpyruvate has become a powerful imaging agent for metabolic neuroimaging due to its central role in glucose and lactate metabolism, ability to cross the blood–brain barrier, and translational utility in neurological disorders. In particular, 1-13Cpyruvate enables an assessment of mitochondrial metabolism in the cerebral cortex through its conversion to 13Cbicarbonate. While it is not yet confirmed that production of 13Cbicarbonate primarily reflects neuronal metabolism, the higher affinity of neuronal transporters for lactate over pyruvate has motivated interest in hyperpolarized lactate as a more physiologic probe of neuronal metabolism. Here, we identify the predominant cellular source of 13Cbicarbonate and evaluate 1-13Clactate as an imaging agent for neuronal metabolic imaging. Ex vivo NMR and mass spectrometry imaging of brain tissue collected after bolus injection of U–13C3pyruvate revealed that pyruvate dehydrogenase dominates pyruvate carboxylase in the cortex, supporting the neuronal origin of 13Cbicarbonate production. Although the bicarbonate fraction among the total 13C products in vivo was higher following hyperpolarized 1-13Clactate injection, the signal sensitivity was markedly reduced due to lactate’s shorter T1 and larger endogenous pool. Isotopomer analysis of brain tissue harvested 2 min after injection of U–13C3pyruvate or U–13C3lactate showed comparable labeling of mitochondrial intermediates. In glioma-bearing rats, in vivo imaging revealed an elevated pyruvate-to-lactate ratio within the tumor, highlighting altered redox and transport dynamics in malignancy. These findings demonstrate that both hyperpolarized 1-13Cpyruvate and 1-13Clactate can effectively probe neuronal and glioma metabolism, although pyruvate outperforms lactate in detecting pyruvate dehydrogenase flux.
Chen et al. (Fri,) studied this question.