Mild experimental ketosis increases brain uptake of 11C-acetoacetate and 18F-fluorodeoxyglucose: a dual-tracer PET imaging study in rats

Nutr Neurosci. 2011 Mar;14(2):51-8. doi: 10.1179/1476830510Y.0000000001.


Brain glucose and ketone uptake was investigated in Fisher rats subjected to mild experimental ketonemia induced by a ketogenic diet (KD) or by 48 hours fasting (F). Two tracers were used, (11)C-acetoacetate ((11)C-AcAc) for ketones and (18)F-fluorodeoxyglucose for glucose, in a dual-tracer format for each animal. Thus, each animal was its own control, starting first on the normal diet, then undergoing 48 hours F, followed by 2 weeks on the KD. In separate rats on the same diet conditions, expression of the transporters of glucose and ketones (glucose transporter 1 (GLUT1) and monocarboxylic acid transporter (MCT1)) was measured in brain microvessel preparations. Compared to controls, uptake of (11)C-AcAc increased more than 2-fold while on the KD or after 48 hours F (P < 0.05). Similar trends were observed for (18)FDG uptake with a 1.9-2.6 times increase on the KD and F, respectively (P < 0.05). Compared to controls, MCT1 expression increased 2-fold on the KD (P < 0.05) but did not change during F. No significant difference was observed across groups for GLUT1 expression. Significant differences across the three groups were observed for plasma beta-hydroxybutyrate (beta-HB), AcAc, glucose, triglycerides, glycerol, and cholesterol (P < 0.05), but no significant differences were observed for free fatty acids, insulin, or lactate. Although the mechanism by which mild ketonemia increases brain glucose uptake remains unclear, the KD clearly increased both the blood-brain barrier expression of MCT1 and stimulated brain (11)C-AcAc uptake. The present dual-tracer positron emission tomography approach may be particularly interesting in neurodegenerative pathologies such as Alzheimer's disease where brain energy supply appears to decline critically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Acetoacetates / pharmacokinetics*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism*
  • Cholesterol / blood
  • Contrast Media / pharmacokinetics
  • Diet, Ketogenic
  • Fasting
  • Fatty Acids, Nonesterified / blood
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Gene Expression Regulation
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glycerol / blood
  • Insulin / blood
  • Ketosis / diagnostic imaging*
  • Ketosis / metabolism*
  • Lactic Acid / blood
  • Male
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • Positron-Emission Tomography / methods
  • Rats
  • Rats, Inbred F344
  • Symporters / genetics
  • Symporters / metabolism
  • Triglycerides / blood


  • Acetoacetates
  • Contrast Media
  • Fatty Acids, Nonesterified
  • Glucose Transporter Type 1
  • Insulin
  • Monocarboxylic Acid Transporters
  • Slc2a1 protein, rat
  • Symporters
  • Triglycerides
  • monocarboxylate transport protein 1
  • Fluorodeoxyglucose F18
  • Lactic Acid
  • Cholesterol
  • Glycerol
  • 3-Hydroxybutyric Acid