title: Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.
abstract: During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT.
  
  
  METHODS
  A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH).
  
  
  RESULTS
  The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed.
  
  
  CONCLUSIONS
  We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases.
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; and.
authors.forename: Anna Christina
authors.initials: AC
authors.lastname: Schacht
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; and Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Sørensen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; and.
authors.forename: Ole Lajord
authors.initials: OL
authors.lastname: Munk
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; and frisch@pet.auh.dk.
authors.forename: Kim
authors.initials: K
authors.lastname: Frisch
mesh_terms: D000818:Animals; D001646:Bile / Q000000981:diagnostic imaging / Q000378:metabolism; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics*; D002779:Cholestasis / Q000000981:diagnostic imaging; D002855:Chromatography, Thin Layer; D005260:Female; D007553:Isotope Labeling; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D034421:Sus scrofa; D013654:Taurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001647:Bile Acids and Salts; D008055:Lipids; D019275:Radiopharmaceuticals; D013654:Taurine
keywords: cholestasis; enterohepatic circulation; lipophilicity; primary and secondary bile acids; taurine conjugation