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

Yu Ouyang, Jeff N. Tinianow, Simon R Cherry, Jan Marik

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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-[18F]fluoroacetate ([18F]FACE), suggesting possible use for specifically imaging glial metabolism. To assess this hypothesis, we evaluated [18F]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 [ 18F]FACE uptake were developed and quantitatively compared. Elevated [18F]FACE uptake was found to be driven primarily by K 1/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 [18F]FACE uptake. We conclude that kinetic modeling of [18F]FACE uptake represents a potentially useful tool for interrogation of glial metabolism.

Original languageEnglish (US)
Pages (from-to)836-844
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume34
Issue number5
DOIs
StatePublished - 2014

Keywords

  • cerebral hypoxia-ischemia
  • fluoroacetate
  • glial metabolism
  • kinetic modeling
  • MRI
  • PET

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology
  • Medicine(all)

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