IN-VIVO PROTEIN-SYNTHESIS RATE DETERMINATION IN PRIMARY OR RECURRENT BRAIN-TUMORS USING L-[1-C-11]-TYROSINE AND PET

The applicability of protein synthesis rate (PSR) determination with L-[1-C-11]tyrosine (C-11-TYR) and PET was assessed in patients suspected of a primary or recurrent brain tumor. Methods: Simultaneous to intravenous injection of 265 MBq of C-11-TYR, dynamic PET acquisition was started and continued for 50 min. Arterial samples were taken and analyzed for C-11-TYR and metabolites. Based on this data, a model was proposed and the corresponding PSR calculated. Results: Plasma metabolites were (CO2)-C-11, C-11-proteins and C-11-L-DOPA, constituting more than 50% of total plasma radioactivity at 40 min postinjection. Plasma (CO2)-C-11 reached a plateau of around 25% of total plasma radioactivity at 20 min postinjection. Plasma C-11-protein was not detected before 10 min postinjection, but increased exponentially afterwards to 20% at 40 min postinjection. Plasma C-11-L-DOPA was the only acid-soluble radioactive metabolite detected and was less than 8% at 40 min postinjection. Using a five-compartment model, it was shown that while the net PSR was dependent on the recycling of amino acids from protein, the amino acid incorporation was not, which was thus used for subsequent analysis. It was found that our curve-fitting results were unreliable due to the exchange of C-11-TYR between plasma and erythrocytes whereas the graphical Patlak-Gjedde analysis is hardly influenced by this transport phenomenon. The average amino acid incorporation rate thus calculated was 0.7 nmole/ml . min for nontumor tissue with a tumor versus nontumor average ratio of 1.7. Conclusion: The assessment of the PSR with TYR-PET is valuable and relatively simple to implement clinically.