In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine

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-to-pyruvate ratio of normal rat tissue measured with hyperpolarized 1-¹³C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized 1-¹³C]pyruvate was injected.