19F nuclear magnetic resonance imaging of drug distribution in vivo: The disposition of an antifolate anticancer drug in mice

The application of 19F nuclear magnetic resonance imaging to the study of drug distribution in vivo is discussed. CB3988 (C2-desamino-C2-methyl-N10-propargyl-2′-trifluoromethyl-5,8-dideazafolic acid) is a fluorinated representative of a class of quinazoline an-tifolates which act as inhibitors of thymidylate synthase and which are being evaluated for the treatment of human cancer. 19 F images were obtained in vivo from the abdomen of mice following intravenous injection of CB3988 (500 mg/kg). Time resolutions of 4 and 20 min were achieved for two- and three-dimensional imaging, respectively. These images were consistent with the presence of high concentrations of drug (up to 26 mg/ml) in the gall bladder, urinary bladder, and small intestine, as confirmed ex vivo by extraction and HPLC analysis. The results indicate the potential value of 19F NMR imaging in pharmacokinetic Studies. © 1991 Academic Press, Inc.