A new hyperpolarized 13C ketone body probe reveals an increase in acetoacetate utilization in the diabetic rat heart

Emerging studies have recently shown the potential importance of ketone bodies in cardio-metabolic health. However, techniques to determine myocardial ketone body utilization in vivo are lacking. In this work, we developed a novel method to assess myocardial ketone body utilization in vivo using hyperpolarized [3-C-13]acetoacetate and investigated the alterations in myocardial ketone body metabolism in diabetic rats. Within a minute upon injection of [3-C-13]acetoacetate, the production of [5-C-13]g lutamate and [1-C-13] acetylcarnitine can be observed real time in vivo. In diabetic rats, the production of [5-C-13]glutamate was elevated compared to controls, while [1-C-13]acetylcarnitine was not different. This suggests an increase in ketone body utilization in the diabetic heart, with the produced acetyl-CoA channelled into the tricarboxylic acid cycle. This observation was corroborated by an increase activity of succinyl-CoA:3-ketoacid-CoAtransferase (SCOT) activity, the rate-limiting enzyme of ketone body utilization, in the diabetic heart. The increased ketone body oxidation in the diabetic hearts correlated with cardiac hypertrophy and dysfunction, suggesting a potential coupling between ketone body metabolism and cardiac function. Hyperpolarized [3-C-13]acetoacetate is a new probe with potential for non-invasive and real time monitoring of myocardial ketone body oxidation in vivo, which offers a powerful tool to follow disease progression or therapeutic interventions.