title: Evaluation of 2-[¹⁸F]fluoroacetate kinetics in rodent models of cerebral hypoxia-ischemia.
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.
authors: Department of Biomedical Engineering, University of California, Davis, California, USA.
authors: Yu
authors: Y
authors: Ouyang
authors: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, California, USA.
authors: Jeff N
authors: JN
authors: Tinianow
authors: Department of Biomedical Engineering, University of California, Davis, California, USA.
authors: Simon R
authors: SR
authors: Cherry
authors: Department of Biomedical Imaging, Genentech, Inc., South San Francisco, California, USA.
authors: Jan
authors: J
authors: Marik
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D005463:Fluoroacetates / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D005463:Fluoroacetates