PET of Glial Metabolism Using 2-18F-Fluoroacetate

Imaging of the glial activation that occurs in response to central nervous system trauma and inflammation could become a powerful technique for the assessment of several neuropathologies. The selective uptake and metabolism of 2-F-18-fluoroacetate (F-18-FAC) in glia may represent an attractive strategy for imaging glial metabolism. Methods: We have evaluated the use of F-18-FAC as a specific PET tracer of glial cell metabolism in rodent models of glioblastoma, stroke, and ischemia-hypoxia. Results: Enhanced uptake of F-18-FAC was observed (6.98 +/- 0.43 percentage injected dose per gram [%ID/g]; tumor-to-normal ratio, 1.40) in orthotopic U87 xenografts, compared with healthy brain tissue. The lesion extent determined by F-18-FAC PET correlated with that determined by MRI (R-2 = 0.934, P = 0.007). After transient middle cerebral artery occlusion in the rat brain, elevated uptake of F-18-FAC (1.00 +/- 0.03 % ID/g; lesion-to-normal ratio, 1.90) depicted the ischemic territory and correlated with infarct volumes as determined by 2,3,5-triphenyltetrazolium chloride staining (R-2 = 0.692, P = 0.010) and with the presence of activated astrocytes detected by anti-glial fibrillary acidic protein. Ischemia-hypoxia, induced by permanent ligation of the common carotid artery with transient hypoxia, resulted in persistent elevation of F-18-FAC uptake within 30 min of the induction of hypoxia. Conclusion: Our data support the further evaluation of F-18-FAC PET for the assessment of glial cell metabolism associated with neuroinflammation.