L-[2-18F]fluorotyrosine (2-18FTyr) was evaluated as a tracer of cerebral protein synthesis for positron emission tomography (PET). Its metabolism in murine cerebrum was studied. The uptake in brain reaches a value of approximately 2% of the injected dose per gram tissue after 60 min. The incorporation of the tracer into tissue proteins was proven by discontinuous SDS gel electrophoresis. The protein bound fraction of tissue activity increased to 84% and 89% after 60 and 120 min p.i., respectively. High performance liquid chromatography analysis showed a concomitant decrease of free 2-18FTyr in tissue with time. The sum of free 2-18FTyr, tRNA-and protein-bound 2-18FTyr in cerebral tissue gave an almost quantitative activity balance of 96 +/- 4% at all times examined. A significant formation of fluorodopa or fluorodopamine must therefore be excluded. This shows that L-[2-18F]fluorotyrosine is a promising tracer for quantitation of protein synthesis rates with PET based on a three-compartment model.
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