Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high sensitivity measurements of 13C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized 13C metabolic imaging thus far has been [1-13C]pyruvate. In preclinical studies, not only is its uptake detected, but also, its intracellular enzymatic conversion to metabolic products including [1-13C]lactate and [1-13C]alanine. However, the ratio of 13C-lactate/13C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-13C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-13C]alanine and monitored the in vivo conversion to [1-13C]pyruvate and then the subsequent conversion to [1-13C]lactate. The intracellular lactate/pyruvate ratio of normal rat tissue measured with hyperpolarized [1-13C]alanine was 4.89 ± 0.61 (mean ± standard error) as opposed to a ratio of 0.41 ± 0.03 when hyperpolarized [1-13C]pyruvate was injected.

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of 13C metabolism in vivo at very high SNR. In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine if the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+181% ± 69%, p = 0.025) was measured when [1-13C]pyruvate was injected after DCA administration, and increased glutamate (+74% ± 23%, p = 0.004), acetoacetate (+504% ± 281%, p = 0.009), and acetylcarnitine (+377% ± 157%, p = 0.003) were detected when [2-13C]pyruvate was used.