Hepatic metabolism of (11)C-methionine and secretion of (11)C-protein measured by PET in pigs.

Hepatic amino acid metabolism and protein secretion are essential liver functions that may be altered during metabolic stress, e.g. after surgery. We wished to develop a dynamic liver PET method using the radiolabeled amino acid (11)C-methionine to examine this question. Eleven 40-kg pigs were allocated to either laparotomy or pneumoperitoneum. 24 hours after surgery a 70-min dynamic PET scanning of the liver with arterial blood sampling was performed immediately after intravenous injection of (11)C-methionine. Time course of arterial plasma (11)C-methionine concentration was used as input function and that of liver tissue (11)C-concentration as output function in an extended Patlak analysis that accounted for irreversible metabolism of (11)C-methionine (hepatic systemic metabolic clearance Kmet) and secretion of (11)C-protein + (11)C-metabolites into blood (rate constant kloss). Appearance of (11)C-proteins in arterial plasma was measured during the experiment. There were no statistically significant differences between the laparotomy group and the pneumoperitoneum group in any of the calculated parameters. Average mean hepatic systemic metabolic clearance Kmet was 0.212 mL plasma/mL liver tissue/min, secretion rate constant from liver to blood kloss 0.0054 min(-1), flux of methionine Fflux 3.59 μmol methionine/mL liver tissue/min, and the appearance rate of (11)C-proteins in plasma Rprot 0.048 kBq/mL plasma/min. There was significant correlation between Kmet and Rprot. In conclusion, the hepatic systemic metabolic clearance of (11)C-methionine was significantly correlated to the appearance rate of (11)C-proteins in plasma. It would be interesting to translate the present method to human studies for the development of a clinical quantitative test of hepatic protein secretion.