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 language | English (US) |
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Pages (from-to) | 836-844 |
Number of pages | 9 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 34 |
Issue number | 5 |
DOIs | |
State | Published - 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)