Evaluation of 2-[¹⁸F]fluoroacetate kinetics in rodent models of cerebral hypoxia-ischemia

J Cereb Blood Flow Metab. 2014 May;34(5):836-44. doi: 10.1038/jcbfm.2014.22. Epub 2014 Feb 12.


Glia account for 90% of human brain cells and have a significant role in brain homeostasis. Thus, specific in vivo imaging markers of glial metabolism are potentially valuable. In the brain, 2-fluoroacetate is selectively taken up by glial cells and becomes metabolically trapped in the tricarboxylic acid cycle. Recent work in rodent brain injury models demonstrated elevated lesion uptake of 2-[(18)F]fluoroacetate ([(18)F]FACE), suggesting possible use for specifically imaging glial metabolism. To assess this hypothesis, we evaluated [(18)F]FACE kinetics in rodent models of cerebral hypoxia-ischemia at 3 and 24 hours post insult. Lesion uptake was significantly higher at 30 minutes post injection (P<0.05). An image-based method for input function estimation using cardiac blood was validated. Analysis of whole blood showed no significant metabolites and plasma activity concentrations of ∼50% that of whole blood. Kinetic models describing [(18)F]FACE uptake were developed and quantitatively compared. Elevated [(18)F]FACE uptake was found to be driven primarily by K₁/k₂ rather than k₃, but changes in the latter were detectable. The two-tissue irreversible uptake model (2T3k) was found to be necessary and sufficient for modeling [(18)F]FACE uptake. We conclude that kinetic modeling of [(18)F]FACE uptake represents a potentially useful tool for interrogation of glial metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain / pathology
  • Fluorine Radioisotopes / metabolism*
  • Fluoroacetates / metabolism*
  • Humans
  • Hypoxia-Ischemia, Brain / diagnosis
  • Hypoxia-Ischemia, Brain / diagnostic imaging*
  • Hypoxia-Ischemia, Brain / metabolism
  • Kinetics
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Positron-Emission Tomography*
  • Rats
  • Rats, Sprague-Dawley


  • Fluorine Radioisotopes
  • Fluoroacetates