Biological evaluation of 2'-[18F]fluoroflumazenil ([18F]FFMZ), a potential GABA receptor ligand for PET

Nucl Med Biol. 2004 Feb;31(2):291-5. doi: 10.1016/j.nucmedbio.2003.09.003.

Abstract

[(11)C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA(A) ligand for PET so far. To overcome half life disadvantages of (11)C a [(18)F]-labeled flumazenil derivative, 2'-[(18)F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA(A) receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [(3)H]flumazenil binding from membrane GABA(A) receptors with an IC(50)value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [(18)F]FFMZ for PET imaging of the GABA-ergic system.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Drug Evaluation, Preclinical
  • Flumazenil / analogs & derivatives*
  • Flumazenil / pharmacokinetics*
  • Fluorine Radioisotopes / pharmacokinetics
  • Ligands
  • Male
  • Metabolic Clearance Rate
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA / metabolism*
  • Receptors, GABA-A / metabolism
  • Tissue Distribution

Substances

  • 2'-fluoroflumazenil
  • Fluorine Radioisotopes
  • Ligands
  • Radiopharmaceuticals
  • Receptors, GABA
  • Receptors, GABA-A
  • Flumazenil