In vivo magnetic resonance imaging to detect biliary excretion of 19F-labeled drug in mice

Abstract

Isoflurane is an inhaled halogenated hydrocarbon anesthetic commonly used for animal research. In our quest to develop a method for measuring bile acid transport in live animals using 19F magnetic resonance (MR) imaging, it occurred to us that isoflurane, which contains five fluorines per molecule and is probably widely distributed, would provide an excellent test drug to evaluate the merits of this approach. Experiments in 20- to 28-g male C57BL/6 mice were performed using a horizontal bore scanner with a 30-mm 19F/ 1H dual-tuned surface coil used to transmit and receive radiofrequency signals at 300.28 MHz for 1H and 282.55 MHz for 19F nuclei. Proton MR imaging was used to identify the mouse gallbladder in vivo, which was verified by anatomical dissection. Subsequent experiments in mice inhaling 1.5% isoflurane for 1 to 2 h revealed robust 19F signals from the gallbladder, verified by overlying 1H and 19F signals. No 19F signal was detected in mice anesthetized with nonhalogenated anesthetics. The presence of isoflurane in gallbladder bile of isoflurane-treated mice was verified using liquid chromatography-mass spectrometry. Gallbladder bile isoflurane content ranged from 3.2 to 4.7 μg. The data presented here provide proof of concept that this novel approach can be used for in vivo measurement of biliary excretion of both existing and novel 19Flabeled drugs. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.