Comparative Evaluation of Hyperpolarized [ 13 C]pyruvate and [ 13 C]lactate for Imaging Neuronal and Glioma Metabolism

作者：Jun Chen, Maheen Zaidi, Jaideep Chaudhary, Zohreh Erfani, Sarah Al Nemri, Erik J. Plautz, Xiaodong Wen, Erin H. Seeley, Brenda Bartnik‐Olson, Ian R. Corbin, Jae Mo Park · 发表于：ACS Sensors · 年份：2025 · DOI：10.1021/acssensors.5c03203 · 被引用次数：4 · 研究领域：Advanced NMR Techniques and Applications、Advanced MRI Techniques and Applications、Neuroscience and Neuropharmacology Research

Glucose and lactate are primary substrates in cerebral energy metabolism. Hyperpolarized [1- 13 C]pyruvate 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- 13 C]pyruvate enables an assessment of mitochondrial metabolism in the cerebral cortex through its conversion to [ 13 C]bicarbonate. While it is not yet confirmed that production of [ 13 C]bicarbonate 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 [ 13 C]bicarbonate and evaluate [1- 13 C]lactate as an imaging agent for neuronal metabolic imaging. Ex vivo NMR and mass spectrometry imaging of brain tissue collected after bolus injection of [U– 13 C 3 ]pyruvate revealed that pyruvate dehydrogenase dominates pyruvate carboxylase in the cortex, supporting the neuronal origin of [ 13 C]bicarbonate production. Although the bicarbonate fraction among the total 13 C products in vivo was higher following hyperpolarized [1- 13 C]lactate injection, the signal sensitivity was markedly reduced due to lactate’s shorter T 1 and larger endogenous pool. Isotopomer analysis of brain tissue harvested 2 min after injection of [U– 13 C 3 ]pyruvate...