title: PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis.
abstract: Normally, the brain's fuel is glucose, but during fasting it increasingly relies on ketones (beta-hydroxybutyrate, acetoacetate, and acetone) produced in liver mitochondria from fatty acid beta-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.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, 3001, 12th Ave. North, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada. Mhamed.Bentourkia@USherbrooke.ca
authors.forename: M'hamed
authors.initials: M
authors.lastname: Bentourkia
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tremblay
authors.forename: Fabien
authors.initials: F
authors.lastname: Pifferi
authors.forename: Jacques
authors.initials: J
authors.lastname: Rousseau
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.forename: Stephen
authors.initials: S
authors.lastname: Cunnane
mesh_terms: D000090:Acetoacetates / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D004032:Diet; D007662:Ketosis / Q000000981:diagnostic imaging* / Q000178:diet therapy* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods* / Q000662:veterinary; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000090:Acetoacetates; D002250:Carbon Radioisotopes; C016635:acetoacetic acid