We developed methods for the preparation of hyperpolarized (HP) sterile [2-C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-C]pyruvate to [2-C]lactate and [5-C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-C]pyruvate to [2-C]lactate conversion rates (k) were measured and showed similar but not identical inter-subject values.
View Article and Find Full Text PDFPurpose: The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors C-lactate and C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes.
Methods: Seven normal rats were studied by MR spectroscopic imaging of both HP C-lactate and C-pyruvate in both normal fed and 24 h fasting states, and seven additional rats were scanned after induction of diabetes by streptozotocin (STZ) with insulin withdrawal. Phosphoenolpyruvate carboxykinase (PEPCK) expression levels were also measured in liver and kidney tissues of the STZ-treated rats.
We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor.
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