title: Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET.
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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  The in vivo kinetics of hepatobiliary secretion of conjugated bile acids can now be determined by dynamic (11)C-CSar PET.
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark michsoer@rm.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Sørensen
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ole Lajord
authors.initials: OL
authors.lastname: Munk
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Nikolaj W
authors.initials: NW
authors.lastname: Ørntoft
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Frisch
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; and.
authors.forename: Kasper Jarlhelt
authors.initials: KJ
authors.lastname: Andersen
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; and.
authors.forename: Frank Viborg
authors.initials: FV
authors.lastname: Mortensen
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Aage Kristian Olsen
authors.initials: AK
authors.lastname: Alstrup
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Ott
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Keiding
mesh_terms: D000818:Animals; D001659:Biliary Tract / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002793:Cholic Acids / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D012521:Sarcosine / Q000031:analogs & derivatives*; D013552:Swine
chemical_list: D002250:Carbon Radioisotopes; D002793:Cholic Acids; C061997:cholylsarcosine; D012521:Sarcosine
keywords: bile salt export pump; functional molecular imaging; hepatic excretory function; in vivo liver kinetics; intrahepatic cholestasis