Study of /sup 11/C-Acetoacetate Uptake by Rat Heart and Brain Using Small Animal PET Imaging

Normally the brain almost exclusively uses glucose as a fuel but during fasting it can rely on the increased supply of ketones (beta-hydroxybutyrate, acetoacetate and acetone) produced in liver mitochondria from fatty acid beta-oxidation. Raised blood ketones produced on a very high fat ketogenic diet can significantly reduce seizures in children. Ketones also have other ´protective´ effects on the brain but their metabolism by the brain is still poorly understood. The aim of the present work was to assess the brain uptake of ¹¹C-acetoacetate using positron emission tomography (PET) imaging. In order to vary plasma ketones, we used rats (3 groups of 4 rats) under three dietary conditions - control diet (high carbohydrate; low plasma ketones), fat-rich ketogenic diet (moderate plasma ketones), and 48 h fasting (moderate plasma ketones). Tissue perfusion of the tracer and oxygen consumption were measured in heart and brain. In brain but not heart, the ketogenic diet enhanced tracer perfusion and oxygen consumption relative to the two other diets. Our data show that the brain´s ability to utilize increased availability of blood ketones may relate in some way to concurrent glucose availability.