期刊
MOLECULAR PHARMACEUTICS
卷 11, 期 5, 页码 1575-1582出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp400740c
关键词
Bile acid transport; fluorine MRI; bile acid malabsorption; enterohepatic circulation
资金
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [DK-093406, DK-067872, DK047987, DK-081479]
- National Cancer Institute [CA-120407]
- Food and Drug Administration [U01FD004320]
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. F-19 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 F-19 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 F-19 MM. Fluorinated bile acid analogues have potential as tools to measure and detect abnormal bile acid transport by MRI.
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