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-(18)F-fluoroacetate ((18)F-FAC) in glia may represent an attractive strategy for imaging glial metabolism.


METHODS
We have evaluated the use of (18)F-FAC as a specific PET tracer of glial cell metabolism in rodent models of glioblastoma, stroke, and ischemia-hypoxia.


RESULTS
Enhanced uptake of (18)F-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 (18)F-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 (18)F-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 (18)F-FAC uptake within 30 min of the induction of hypoxia.


CONCLUSIONS
Our data support the further evaluation of (18)F-FAC PET for the assessment of glial cell metabolism associated with neuroinflammation.
Marik
Jan
J
Biomedical Imaging, Genentech Inc., One DNA Way, Mailstop 228, South San Francisco, CA 94080, USA. marik.jan@gene.com
Ogasawara
Annie
A
Martin-McNulty
Baby
B
Ross
Jed
J
Flores
Judith E
JE
Gill
Herman S
HS
Tinianow
Jeff N
JN
Vanderbilt
Alexander N
AN
Nishimura
Merry
M
Peale
Franklin
F
Pastuskovas
Cinthia
C
Greve
Joan M
JM
van Bruggen
Nicholas
N
Williams
Simon P
SP
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D005462:Fluorine Radioisotopes; D005463:Fluoroacetates; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar
D005462:Fluorine Radioisotopes; D005463:Fluoroacetates; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18