F-19 NUCLEAR-MAGNETIC-RESONANCE IMAGING OF DRUG DISTRIBUTION INVIVO - 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‐N 10‐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. Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company