Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

J Nucl Med. 2016 Jun;57(6):961-6. doi: 10.2967/jnumed.115.171579. Epub 2016 Mar 10.

Abstract

The aim of this study was to develop a method for the quantification of hepatobiliary uptake and secretion of conjugated bile acids with PET and the (11)C-labeled conjugated bile acid analog [N-methyl-(11)C]cholylsarcosine ((11)C-CSar).

Methods: Six pigs (13 experiments) underwent dynamic (11)C-CSar PET of the liver with simultaneous measurements of hepatic blood perfusion and (11)C-CSar concentrations in arterial, portal, and hepatic venous blood. In 3 pigs (7 experiments), bile was collected from a catheter in the common hepatic duct. PET data were analyzed with a 2-tissue compartmental model with calculation of rate constants for the transport of (11)C-CSar among blood, hepatocytes, and intra- and extrahepatic bile ducts. PET results were validated against invasive blood and bile measurements.

Results: The directly measured rate of secretion of (11)C-CSar into bile was equal to the rate of removal from blood at steady state. Accordingly, hepatocytes did not accumulate bile acids but simply facilitated the transport of bile acids from blood to bile against a measured concentration gradient of 4,000. The rate constant for the secretion of (11)C-CSar from hepatocytes into bile in experiments with a catheter in the common hepatic duct was 25% of that in experiments without a catheter (P < 0.05); we interpreted this result to be mild cholestasis caused by the catheter. The catheter caused an increased backflux of (11)C-CSar from hepatocytes to blood, and hepatic blood flow was 25% higher than in experiments without the catheter. The capacity for the overall transport of (11)C-CSar from blood to bile, as quantified by intrinsic clearance, was significantly lower in experiments with the catheter than in those without the catheter (P < 0.001). PET and blood measurements correlated significantly (P < 0.05).

Conclusion: The in vivo kinetics of hepatobiliary secretion of conjugated bile acids can now be determined by dynamic (11)C-CSar PET.

Keywords: bile salt export pump; functional molecular imaging; hepatic excretory function; in vivo liver kinetics; intrahepatic cholestasis.

MeSH terms

  • Animals
  • Biliary Tract / diagnostic imaging*
  • Biliary Tract / metabolism*
  • Cholic Acids / metabolism*
  • Female
  • Kinetics
  • Liver / diagnostic imaging*
  • Liver / metabolism*
  • Positron-Emission Tomography*
  • Sarcosine / analogs & derivatives*
  • Swine

Substances

  • Cholic Acids
  • cholylsarcosine
  • Sarcosine