Uptake of F-18-fluoroethyl-L-tyrosine and H-3-L-methionine in focal cortical ischemia

Abstract

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Objectives: C-11-methionine (MET) is particularly useful in brain tumor diagnosis but unspecific uptake e.g. in cerebral ischemia has been reported (1). The F-18-labeled amino acid O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) shows a similar clinical potential as MET in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of FET and H-3-MET in focal cortical ischemia in rats by dual tracer autoradiography.

Methods: Focal cortical ischemia was induced in 12 Fisher CDF rats using the photothrombosis model (PT). One day (n=3) , two days (n=5) and 7 days (n=4) after induction of the lesion FET and H-3-MET were injected intravenously. One hour after tracer injection animals were killed, the brains were removed immediately and frozen in 2-methylbutane at -50°C. Brains were cut in coronal sections (thickness: 20 µm) and exposed first to H-3 insensitive photoimager plates to measure FET distribution. After decay of F-18 the distribution of H-3-MET was determined. The autoradiograms were evaluated by regions of interest (ROIs) placed on areas with increased tracer uptake in the PT and the contralateral brain. Lesion to brain ratios (L/B) were calculated by dividing the mean uptake in the lesion and the brain. Based on previous studies in gliomas a L/B ratio > 1.6 was considered as pathological for FET.

Results: Variable increased uptake of both tracers was observed in the PT and its demarcation zone at all stages after PT. The cut-off level of 1.6 for FET was exceeded in 9/12 animals. One day after PT the L/B ratios were 2.0 ± 0.6 for FET vs. 2.1 ± 1.0 for MET (mean ± SD); two days after lesion 2.2 ± 0.7 for FET vs. 2.7 ± 1.0 for MET and 7 days after lesion 2.4 ± 0.4 for FET vs. 2.4 ± 0.1 for MET. In single cases discrepancies in the uptake pattern of FET and MET were observed.

Conclusions: FET like MET may exhibit significant uptake in infarcted areas or the immediate vincinity which has to be considered in the differential diagnosis of unkown brain lesions. The discrepancies in the uptake pattern of FET and MET in some cases indicates either differences in the transport mechanisms of both amino acids or a different affinity for certain cellular components.