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

Magn Reson Med. 1991 Jan;17(1):189-96. doi: 10.1002/mrm.1910170122.

Abstract

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 antifolates which act as inhibitors of thymidylate synthase and which are being evaluated for the treatment of human cancer. 19F 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Fluorine
  • Folic Acid / administration & dosage
  • Folic Acid / analogs & derivatives*
  • Folic Acid / pharmacokinetics
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / pharmacokinetics*
  • Fourier Analysis
  • Gallbladder / metabolism
  • Intestine, Small / metabolism
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Time Factors
  • Tissue Distribution
  • Urinary Bladder / metabolism

Substances

  • Antineoplastic Agents
  • Folic Acid Antagonists
  • CB 3988
  • Fluorine
  • Folic Acid