Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

Nucl Med Biol. 2005 Feb;32(2):109-16. doi: 10.1016/j.nucmedbio.2004.11.001.

Abstract

A straightforward method for the preparation of no-carrier-added (n.c.a.) [18F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K18F/kryptofix complex in DMF at 160 degrees C for 30 min and equimolar ratio [K/K2.2.2]+18F-/precursor. Under these conditions, an 18F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [18F]flumazenil as for [11C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [18F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Flumazenil / analogs & derivatives*
  • Flumazenil / chemistry
  • Flumazenil / pharmacokinetics
  • Humans
  • In Vitro Techniques
  • Isotope Labeling / methods
  • Macaca fascicularis
  • Metabolic Clearance Rate
  • Organ Specificity
  • Positron-Emission Tomography / methods*
  • Radiation Dosage
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, GABA-A / metabolism*
  • Tissue Distribution

Substances

  • Radiopharmaceuticals
  • Receptors, GABA-A
  • 5-(2'-fluoroethyl)flumazenil
  • Flumazenil