title: Design and characterization of a novel fluorinated magnetic resonance imaging agent for functional analysis of bile Acid transporter activity.
abstract: OBJECTIVE
  To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice.
  
  
  METHODS
  Target compound CA-lys-TFA was synthesized and tested for affinity toward the apical sodium dependent bile acid transporter (hASBT) and the Na+/taurocholate cotransporting polypeptide (hNTCP). In a pilot study, fasted mice were gavaged with vehicle control, 150 mg/kg or 300 mg/kg CA-lys-TFA. CA-lys-TFA in gallbladder, liver and plasma at t = 5 h was quantified. Additionally, a 24-h time course (24 mice across eight time points) was studied using 50 mg/kg CA-lys-TFA.
  
  
  RESULTS
  CA-lys-TFA was a potent substrate of hASBT (Kt = 39.4 μM, normalized Vmax = 0.853) and hNTCP (Kt = 8.99 μM, normalized Vmax = 0.281). (19)F MRI phantom imaging showed linear signal-concentration dependence. In vivo studies showed that rapid accumulation of CA-lys-TFA in the gallbladder was maximal within 4-7 h.
  
  
  CONCLUSIONS
  These findings suggest that CA-lys-TFA, a fluorinated non-radioactive bile acid analogue, has potential for use in MRI to measure in vivo bile acid transport and diagnose bile acid malabsorption and other conditions associated with impaired bile acid transport.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
authors: Diana
authors: D
authors: Vivian
authors: Kunrong
authors: K
authors: Cheng
authors: Sandeep
authors: S
authors: Khurana
authors: Su
authors: S
authors: Xu
authors: Valerie
authors: V
authors: Whiterock
authors: Drew
authors: D
authors: Witter
authors: Kimberley A
authors: KA
authors: Lentz
authors: Kenneth S
authors: KS
authors: Santone
authors: Jean-Pierre
authors: JP
authors: Raufman
authors: James E
authors: JE
authors: Polli
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis* / Q000138:chemical synthesis / Q000378:metabolism*; D002460:Cell Line; D005704:Gallbladder / Q000378:metabolism*; D054879:Halogenation; D006801:Humans; D008099:Liver / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D013270:Stomach / Q000648:ultrastructure; D027981:Symporters / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter