Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, ¹¹C-acetoacetate (¹¹C-AcAc), in the heart and kidney compared to ¹¹C-acetate (¹¹C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of ¹¹C-Ac was higher compared to ¹¹C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of ¹¹C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with ¹¹C-Ac. This suggests an equilibrium of ¹¹C-AcAc with the other ketone, ¹¹C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of ¹¹C-AcAc is different compared to ¹¹C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs.