Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia.
Amino acids such as [(11)C-methyl]l-methionine are particularly useful in brain tumor diagnosis, but unspecific uptake (e.g., in cerebral ischemia) has been reported. O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) shows a clinical potential similar to that of l-methionine (MET) in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of [(18)F]FET and [(3)H]MET in focal cortical ischemia in rats by dual-tracer autoradiography.


METHODS
Focal cortical ischemia was induced in 25 CDF rats using the photothrombosis (PT) model. At different time points up to 6 weeks after the induction of PT, [(18)F]FET and [(3)H]MET were injected intravenously. Additionally, contrast-enhanced magnetic resonance imaging (MRI) was performed in 10 animals. One hour after tracer injection, brains were cut in coronal sections and evaluated by dual-tracer autoradiography. Lesion-to-brain (L/B) ratios were calculated by dividing the maximal uptake in the lesion by the mean uptake in the brain. An L/B ratio of >2.0 was considered indicative of pathological uptake. Histological slices were stained by cresyl violet and supplemented by immunostainings for glial fibrillary acidic protein (GFAP) and CD68 in selected cases.


RESULTS
A variably increased uptake of both tracers was observed in the PT lesion and its demarcation zone up to 7 days after PT for [(18)F]FET and up to 6 weeks for [(3)H]MET. The cutoff level of 2.0 was exceeded in 12/25 animals for [(18)F]FET and in 18/25 animals for [(3)H]MET. Focally increased tracer uptake matched contrast enhancement in MRI in 3/10 cases for [(18)F]FET and in 5/10 cases for [(3)H]MET. Immunohistochemical staining in lesions with differential uptake of [(18)F]FET and [(3)H]MET revealed that selective uptake of [(18)F]FET was associated with GFAP-positive astrogliosis while selective [(3)H]MET uptake correlated with CD68-positive macrophage infiltration.


CONCLUSIONS
[(18)F]FET, like [(3)H]MET, may exhibit significant uptake in the periphery of cortical infarctions, which has to be considered in the differential diagnosis of unknown brain lesions. There are discrepancies between [(18)F]FET and [(3)H]MET uptake in the area of infarctions that appear to be caused by the preferential uptake of [(18)F]FET in reactive astrocytes versus the preferential uptake of [(3)H]MET in macrophages.
Salber
Dagmar
D
Department of Medicine, Institute of Neuroscience and Biophysics, Research Center Jülich, PO Box 1913, D-52425 Jülich, Germany.
Stoffels
Gabriele
G
Pauleit
Dirk
D
Reifenberger
Guido
G
Sabel
Michael
M
Shah
Nadim Jon
NJ
Hamacher
Kurt
K
Coenen
Heinz H
HH
Langen
Karl-Josef
KJ
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply*; D005462:Fluorine Radioisotopes; D008297:Male; D008715:Methionine / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D014316:Tritium; D014443:Tyrosine; D008715:Methionine