Vivian Diana, Cheng Kunrong, Khurana Sandeep, Xu Su, Kriel Edwin H, Dawson Paul A, Raufman Jean-Pierre, Polli James E
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21230, United States.
Mol Pharm. 2014 May 5;11(5):1575-82. doi: 10.1021/mp400740c. Epub 2014 Apr 18.
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. (19)F 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 (19)F 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 (19)F MRI. Fluorinated bile acid analogues have potential as tools to measure and detect abnormal bile acid transport by MRI.
设计并合成了一种新型三氟化胆酸衍生物CA-lys-TFA，用作通过磁共振成像（MRI）无创测量胆汁酸转运的工具。在本研究中，在小鼠体内研究了CA-lys-TFA通过MRI测量胆汁酸转运的性能。使用MRI和液相色谱/串联质谱法定量胆囊中CA-lys-TFA的含量。将野生型（WT）C57BL/6J小鼠的结果与缺乏回肠胆汁酸转运体Asbt表达的小鼠的结果进行比较。口服150mg/kg CA-lys-TFA 7小时后，MRI可重复检测到WT小鼠胆囊发出的（19）F信号。给予相同剂量的Asbt缺陷小鼠通过MRI检测不到（19）F信号，并且胆囊胆汁中CA-lys-TFA水平比WT动物低30倍。据我们所知，这是首次使用（19）F MRI对口服吸收药物进行体内成像的报告。氟化胆汁酸类似物有潜力作为通过MRI测量和检测异常胆汁酸转运的工具。
