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Am J Physiol Endocrinol Metab 296: E796-E801, 2009. First published January 27, 2009; doi:10.1152/ajpendo.90644.2008
0193-1849/09 $8.00
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PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis

M'hamed Bentourkia,1 Sébastien Tremblay,1,4 Fabien Pifferi,2,4 Jacques Rousseau,1 Roger Lecomte,1 and Stephen Cunnane2,3,4

Departments of 1Nuclear Medicine and Radiobiology, 2Medicine, and 3Physiology and Biophysics, and 4Research Center on Aging, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Submitted 31 July 2008 ; accepted in final form 26 January 2009

Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (β-hydroxybutyrate, acetoacetate, and acetone) produced in liver mitochondria from fatty acid β-oxidation. Although moderately raised blood ketones produced on a very high fat ketogenic diet have important clinical effects on the brain, including reducing seizures, ketone metabolism by the brain is still poorly understood. The aim of the present work was to assess brain uptake of carbon-11-labeled acetoacetate (11C-acetoacetate) by positron emission tomography (PET) imaging in the intact, living rat. To vary plasma ketones, we used three dietary conditions: high carbohydrate control diet (low plasma ketones), fat-rich ketogenic diet (raised plasma ketones), and 48-h fasting (raised plasma ketones). 11C-acetoacetate metabolism was measured in the brain, heart, and tissue in the mouth area. Using 11C-acetoacetate and small animal PET imaging, we have noninvasively quantified an approximately seven- to eightfold enhanced brain uptake of ketones on a ketogenic diet or during fasting. This opens up an opportunity to study brain ketone metabolism in humans.

positron emission tomography; ketogenic diet; ketone bodies


Address for reprint requests and other correspondence: M. Bentourkia, Dept. of Nuclear Medicine and Radiobiology, 3001, 12th Ave. North, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada (e-mail: Mhamed.Bentourkia{at}USherbrooke.ca)






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