Abstract
An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n = 3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4-10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA...Continue Reading
References
Mar 12, 2005·The AAPS Journal·Giulia GhibelliniKim L R Brouwer
Apr 4, 2007·Pharmaceutical Research·Waddah A Alrefai, Ravinder K Gill
Feb 5, 2008·Clinics in Liver Disease·Gernot Zollner, Michael Trauner
May 20, 2008·Cellular and Molecular Life Sciences : CMLS·A F Hofmann, L R Hagey
Sep 20, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yazen AlnoutiCurtis D Klaassen
Nov 7, 2008·Angewandte Chemie·Philip W MillerAntony D Gee
Apr 12, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Manmeet S PaddaJames L Boyer
Mar 29, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kim FrischSusanne Keiding
Jul 17, 2012·Clinics and Research in Hepatology and Gastroenterology·Ralf KubitzDieter Häussinger
Aug 10, 2013·European Journal of Clinical Investigation·Christoph JüngstFrank Lammert
Dec 18, 2013·Molecular Pharmaceutics·Pablo M GonzálezJames E Polli
Mar 5, 2014·Expert Opinion on Drug Metabolism & Toxicology·Manuela de Lima Toccafondo Vieira, Carlos Alberto Tagliati
Apr 30, 2014·Nuclear Medicine and Biology·Lina JiaLan Zhang
Dec 3, 2014·International Journal of Pharmaceutics·Zhongqi DongJames E Polli
Dec 25, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anna Christina SchachtKim Frisch
Dec 25, 2016·Bioorganic & Medicinal Chemistry·Andrea TestaMatteo Zanda
Jan 7, 2017·PloS One·Takahiro SugaNariyasu Mano
Mar 9, 2017·PloS One·Stef De LombaerdeFilip De Vos