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

TY - JOUR

T1 - Hepatic metabolism of 11C-methionine and secretion of 11C-protein measured by PET in pigs

AU - Horsager, Jacob

AU - Lausten, Susanne Bach

AU - Bender, Dirk

AU - Munk, Ole Lajord

AU - Keiding, Susanne

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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 11C-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 11C-methionine. Time course of arterial plasma 11C-methionine concentration was used as input function and that of liver tissue 11C-concentration as output function in an extended Patlak analysis that accounted for irreversible metabolism of 11C-methionine (hepatic systemic metabolic clearance Kmet) and secretion of 11C-protein + 11C-metabolites into blood (rate constant kloss). Appearance of 11C-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 11C-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 11C-methionine was significantly correlated to the appearance rate of 11C-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.

AB - 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 11C-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 11C-methionine. Time course of arterial plasma 11C-methionine concentration was used as input function and that of liver tissue 11C-concentration as output function in an extended Patlak analysis that accounted for irreversible metabolism of 11C-methionine (hepatic systemic metabolic clearance Kmet) and secretion of 11C-protein + 11C-metabolites into blood (rate constant kloss). Appearance of 11C-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 11C-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 11C-methionine was significantly correlated to the appearance rate of 11C-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.

KW - Journal Article

M3 - Journal article

C2 - 28913155

SN - 2160-8407

VL - 7

SP - 167

EP - 173

JO - American Journal of Nuclear Medicine and Molecular Imaging

JF - American Journal of Nuclear Medicine and Molecular Imaging

IS - 4

ER -