Assessment of Cardiac TCA Cycle Activity with Hyperpolarized [1-13C]Acetyl-L-Carnitine

Hyperpolarized [1-13C]acetyl-L-carnitine was developed as a probe to investigate cardiac TCA cycle activity in vivo. [5-13C]Glutamate, which is produced via TCA cycle intermediate a-ketoglutarate, was successfully observed in rat heart under both fasting and fed conditions. Importantly, although pyruvate dehydrogenase activity is decreased in the fasted state, [5-13C]glutamate remained observable at appreciable levels, suggesting that [1-13C]acetyl-L-carnitine provides complementary information relative to standard assessments of pyruvate oxidation with hyperpolarized [1-13C]pyruvate. In turn, this novel probe may facilitate comprehensive metabolic analyses of acetyl-CoA uptake by the TCA cycle for various cardiac applications.