A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET

We studied the potential of L-[1-C-11]tyrosine ([1-C-11]Tyr) and L-[methyl-C-11]methionine ([Me-C-11]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. Methods: In the liver and plasma of control and cycloheximide-treated mice injected with [1-C-14]Tyr and [Me-H-3]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with C-11-labeled analogs and PET. Results: In mice, liver uptake of [Me-H-3]Met was over twice as large as that of [1-C-14]Tyr. Similar uptake patterns of the C-11-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, similar to 69%-73% of the C-14 was detected in the protein fraction, whereas similar to 65%-70% of the H-3 was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were similar to 73%-76% for C-14 and similar to 36%-46% for H-3. Gel-filtration analysis suggested that 80% of the C-14-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide the liver uptake of the [1-C-14]Tyr and the protein-incorporation of C-14 in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-H-3]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. Conclusion: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-C-11]Met mainly reflects phospholipid synthesis through the transmethylation process.