In vivo performance of a novel fluorinated magnetic resonance imaging agent for functional analysis of bile acid transport

Diana Vivian, Kunrong Cheng, Sandeep Khurana, Su Xu, Edwin H. Kriel, Paul A. Dawson, Jean Pierre Raufman, James E. Polli

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16 Scopus citations

Abstract

A novel trifluorinated cholic acid derivative, CA-lys-TFA, was designed and synthesized for use as a tool to measure bile acid transport noninvasively using magnetic resonance imaging (MRI). In the present study, the in vivo performance of CA-lys-TFA for measuring bile acid transport by MRI was investigated in mice. Gallbladder CA-lys-TFA content was quantified using MRI and liquid chromatography/tandem mass spectrometry. Results in wild-type (WT) C57BL/6J mice were compared to those in mice lacking expression of Asbt, the ileal bile acid transporter. 19F signals emanating from the gallbladders of WT mice 7 h after oral gavage with 150 mg/kg CA-lys-TFA were reproducibly detected by MRI. Asbt-deficient mice administered the same dose had undetectable 19F signals by MRI, and gallbladder bile CA-lys-TFA levels were 30-fold lower compared to WT animals. To our knowledge, this represents the first report of in vivo imaging of an orally absorbed drug using 19F MRI. Fluorinated bile acid analogues have potential as tools to measure and detect abnormal bile acid transport by MRI.

Original languageEnglish (US)
Pages (from-to)1575-1582
Number of pages8
JournalMolecular Pharmaceutics
Volume11
Issue number5
DOIs
StatePublished - May 5 2014

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Keywords

  • Bile acid transport
  • bile acid malabsorption
  • enterohepatic circulation
  • fluorine MRI

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Vivian, D., Cheng, K., Khurana, S., Xu, S., Kriel, E. H., Dawson, P. A., Raufman, J. P., & Polli, J. E. (2014). In vivo performance of a novel fluorinated magnetic resonance imaging agent for functional analysis of bile acid transport. Molecular Pharmaceutics, 11(5), 1575-1582. https://doi.org/10.1021/mp400740c