Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia

Amino acids such as [11C-methyl]l-methionine are particularly useful in brain tumor diagnosis, but unspecific uptake (e.g., in cerebral ischemia) has been reported. O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]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 [18F]FET and [3H]MET in focal cortical ischemia in rats by dual-tracer autoradiography.MethodsFocal 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, [18F]FET and [3H]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.ResultsA variably increased uptake of both tracers was observed in the PT lesion and its demarcation zone up to 7 days after PT for [18F]FET and up to 6 weeks for [3H]MET. The cutoff level of 2.0 was exceeded in 12/25 animals for [18F]FET and in 18/25 animals for [3H]MET. Focally increased tracer uptake matched contrast enhancement in MRI in 3/10 cases for [18F]FET and in 5/10 cases for [3H]MET. Immunohistochemical staining in lesions with differential uptake of [18F]FET and [3H]MET revealed that selective uptake of [18F]FET was associated with GFAP-positive astrogliosis while selective [3H]MET uptake correlated with CD68-positive macrophage infiltration.Conclusions[18F]FET, like [3H]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 [18F]FET and [3H]MET uptake in the area of infarctions that appear to be caused by the preferential uptake of [18F]FET in reactive astrocytes versus the preferential uptake of [3H]MET in macrophages.