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Metabolic Studies with L-[1-¹⁴C]Tyrosine for the Investigation of a Kinetic Model to Measure Protein Synthesis Rates with PET

Department of Nuclear Medicine, University Hospital, Groningen, The Netherlands

Correspondence: For reprints contact: Prof. Dr. W. Vaalburg, Dept. of Nuclear Medicine, University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands.

ABSTRACT

To evaluate a kinetic model for measuring protein synthesis rates by positron emission tomography (PET) in neoplastic and normal tissue, metabolic studies with L-[1-¹⁴C]tyrosine were carried out. As an animal model, rats bearing Walker 256 carcinosarcoma were used. Within 60 min after injection, several metabolic parameters were measured. The highest radioactivity uptake, expressed as the differential absorption ratio, was found in pancreas, followed by liver, tumor, and brain. A rapid decarboxylation was observed during the first 15 min. After 60 min, 7.4% of the total injected ¹⁴C was expired as ¹⁴CO₂. In plasma a significant amount of [¹⁴C]bicarbonate was detected, but in tissue the amount was negligible. Protein incorporation increased with time. The incorporation rate was the highest in the liver followed by pancreas, tumor, and brain tissues. At 60 min after injection, more than 80% of the ¹⁴C in tissue was protein bound. In plasma after a rapid clearance during the first 15 min, the total ¹⁴C level increased rapidly and paralleled the increase of protein-bound ¹⁴C. As nonprotein [¹⁴C]metabolites, in plasma, tumor and brain tissues, p-hydroxyphenylpyruvic acid, p-hydroxyphenyllactic acid, and unidentified metabolites were observed by high performance liquid chromatography. The formation of ¹⁴C-labeled 3,4-dihydroxyphenylalanine was found to be negligible. The total amount of these nonprotein metabolites increased with time. At 60 min after injection the percentages of the total nonprotein metabolites and [¹⁴C]bicarbonate were only 5.0%, 1.9%, and 3.7% in plasma, tumor and brain tissue, respectively. From our data it is concluded that [¹¹C]carboxylic-labeled tyrosine would be a suitable radiopharmaceutical for measuring protein synthesis rates in neoplastic and normal tissue by PET.

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