Binding of 5-(2′-[18F]fluoroenthyl)flumazenil to central benzodiazepine receptors measured in living baboon by positron emission tomography

https://doi.org/10.1016/0014-2999(92)90153-UGet rights and content

Abstract

5-(2′-[18F]Fluoroethyl)flumazenil ([18F]FEF), a fluorine-18-labeled analogue of the benzodiazepine antagonist flumazenil, was evaluated for use with positron emission tomography (PET). PET imaging of a baboon after i.v. injection of [18F]FEF showed that the radiofluorinated ligand rapidly localized in vivo within benzodiazepine receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Coinjection of unlabeled flumazenil (0.55 mg/kg i.v.) abolished the heterogeneous cerebral distribution of the tracer; receptor-specific uptake was reduced by approximately 95%. The fluorinated benzodiazepine antagonist was degraded in vivo only to polar radiometabolites that do not cross the blood-brain barrier. [18F]FEF has advantages over existing PET radiopharmaceuticals, and is a promising radioligand for non-invasive evaluation of central benzodiazepine receptor binding in vivo.

References (39)

  • Y. Samson et al.

    Kinetics and displacement of [11C]Ro 15-1788, a benzodiazepine antagonist, studied in human brain in vivo by positron emission tomography

    Eur. J. Pharmacol.

    (1985)
  • R.-R. Teng et al.

    The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands

    Nucl. Med. Biol.

    (1990)
  • M. Zell et al.

    Highly sensitive assay of a benzodiazepine antagonist in plasma by capillary gas chromatography with nitrogen-selective detection

    J. Chromatogr. Biomed. Appl.

    (1986)
  • S.C. Cheetham et al.

    GABAA and benzodiazepine binding sites in the cortex of depressed suicide victims

    Br. J. Pharmacol.

    (1985)
  • R. Davis et al.

    A Stereotaxic Atlas of the Brain of the Baboon

    (1968)
  • P.D. Griffeths et al.

    Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease

    J. Neurol. Sci.

    (1990)
  • St.J. Kish et al.

    Benzodiazepine receptor binding in cerebellar cortex: observations in olivopontocerebellar atrophy

    J. Neurochem.

    (1984)
  • C. Loc'h et al.

    [11C]-Flumazenil metabolites: measurements of unchanged ligand in plasma using thin layer chromatography and rapid liquid chromatography

    J. Lab. Comp. Radiopharm.

    (1991)
  • M.A. Mintun et al.

    A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography

    Ann. Neurol.

    (1984)
  • Cited by (0)

    View full text