Evaluation of 2-[18F]fluoroacetate Kinetics in Rodent Models of Cerebral Hypoxia–Ischemia. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Ouyang, Yu; Tinianow, Jeff N; Cherry, Simon R; Marik, Jan
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 34:Issue 5(2014)
• Page Start: 836
• Page End: 844
• Publication Date: 2014-05
• Subjects: cerebral hypoxia-ischemia -- fluoroacetate -- glial metabolism -- kinetic modeling -- MRI -- PET; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2014.22
• Languages: English
• ISSNs: 0271-678X

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-[ 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.