ArticlePloS one2017
Synthesis, in vitro and in vivo evaluation of 3β-[18F]fluorocholic acid for the detection of drug-induced cholestasis in mice.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD).Bioconjugate chemistry · 2024Article
- Integrated Small Animal PET/CT/RT with Onboard PET/CT Image Guidance for Preclinical Radiation Oncology Research.Tomography (Ann Arbor, Mich.) · 2023Article
- Use of imaging to assess the activity of hepatic transporters.Expert opinion on drug metabolism & toxicology · 2020Review
- Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective.Clinical pharmacology and therapeutics · 2018Review
- Preclinical Evaluation of [Contrast media & molecular imaging · 2018Article
- Evaluating Hepatobiliary Transport withContrast media & molecular imaging · 2018Article
- Quantitative PET of liver functions.American journal of nuclear medicine and molecular imaging · 2018Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDrug-induced cholestasis is a liver disorder that might be caused by interference of drugs with the hepatobiliary bile acid transporters. It is important to identify this interference early on in drug development. In this work, Positron Emission Tomography (PET)-imaging with a 18F labeled bile acid analogue was introduced to detect disturbed hepatobiliary transport of bile acids.
methods3β-[18F]fluorocholic acid ([18F]FCA) was prepared by nucleophilic substitution of a mesylated precursor with [18F]fluoride, followed by deprotection with sodium hydroxide. Transport of [18F]FCA was assessed in vitro using CHO-NTCP, HEK-OATP1B1, HEK-OATP1B3 transfected cells and BSEP & MRP2 membrane vesicles. Investigation of [18F]FCA metabolites was performed with primary mouse hepatocytes. Hepatobiliary transport of [18F]FCA was evaluated in vivo in wild-type, rifampicin and bosentan pretreated FVB-mice by dynamic μPET scanning.
resultsRadiosynthesis of [18F]FCA was achieved in a moderate radiochemical yield (8.11 ± 1.94%; non-decay corrected; n = 10) and high radiochemical purity (>99%). FCA was transported by the basolateral bile acid uptake transporters NTCP, OATP1B1 and OATP1B3. For canalicular efflux, BSEP and MRP2 are the relevant bile acid transporters. [18F]FCA was found to be metabolically stable. In vivo, [18F]FCA showed fast hepatic uptake (4.5 ± 0.5 min to reach 71.8 ± 1.2% maximum % ID) and subsequent efflux to the gallbladder and intestines (93.3 ± 6.0% ID after 1 hour). Hepatobiliary transport of [18F]FCA was significantly inhibited by both rifampicin and bosentan.
conclusionA 18F labeled bile acid analogue, [18F]FCA, has been developed that shows transport by NTCP, OATP, MRP2 and BSEP. [18F]FCA can be used as a probe to monitor disturbed hepatobiliary transport in vivo and accumulation of bile acids in blood and liver during drug development.
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