Radiosynthesis of N-C-11-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT

摘要

During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-C-11-methyl-glycocholic acid-that is, C-11-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-C-11-methyltaurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. Methods: A radiosynthesis of N-C-11-methyl-taurine-conjugated bile acids was developed and used to prepare N-C-11-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 (3 alpha-OH, 7 alpha-OH, 12 alpha-OH), ursodeoxycholic acid (3 alpha-OH, 7 beta-OH), and lithocholic acid (3 alpha-OH). Results: The radiosyntheses of the N-C-11-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-C-11-methyl-taurolithocholic acid into the stomach was observed. Conclusion: We have successfully developed a radiosynthesis of N-C-11-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.