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

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.

[1]  J. Penney,et al.  Benzodiazepine and GABA receptors in early Huntington's disease , 1984, Neurology.

[2]  G. Sedvall,et al.  IN-VIVO DEMONSTRATION OF REDUCED BENZODIAZEPINE RECEPTOR BINDING IN HUMAN EPILEPTIC FOCI , 1988, The Lancet.

[3]  D. Snyder,et al.  Corrections for accidental coincidences and attenuation in maximum-likelihood image reconstruction for positron-emission tomography. , 1991, IEEE transactions on medical imaging.

[4]  M. Ter-pogossian,et al.  PETT VI: A Positron Emission Tomograph Utilizing Cesium Fluoride Scintillation Detectors , 1982, Journal of computer assisted tomography.

[5]  J. Baron,et al.  Regional Specific Binding of [11C]RO 15 1788 to Central Type Benzodiazepine Receptors in Human Brain: Quantitative Evaluation by PET , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  D. Overstreet,et al.  Benzodiazepine receptors: The effect of GABA on their characteristics in human brain and their alteration in Huntington's disease , 1980, Brain Research.

[7]  H. Mohler,et al.  Benzodiazepine receptor: demonstration in the central nervous system , 1977, Science.

[8]  S. Snyder,et al.  Huntington's disease , 1987, Neurology.

[9]  C. Braestrup,et al.  Benzodiazepine receptors in rat brain , 1977, Nature.

[10]  J. Baron,et al.  Cerebral uptake of benzodiazepine measured by positron emission tomography in hepatic encephalopathy. , 1987, The New England journal of medicine.

[11]  S. Kish,et al.  Brain γ-aminobutyric acid and benzodiazepine receptor binding in dialysis encephalopathy , 1985, Neuroscience Letters.

[12]  S. Kish,et al.  Benzodiazepine Receptor Binding in Cerebellar Cortex: Observations in Olivopontocerebellar Atrophy , 1984, Journal of neurochemistry.

[13]  D Comar,et al.  Kinetics and displacement of [11C]RO 15-1788, a benzodiazepine antagonist, studied in human brain in vivo by positron tomography. , 1985, European journal of pharmacology.

[14]  G. Blomqvist,et al.  Cortical Benzodiazepine Receptor Binding in Patients with Generalized and Partial Epilepsy , 1990, Epilepsia.

[15]  F. E. Bloom.  A stereotaxic atlas of the brain of the baboon: (Papio)R. Davis andR. E. Huffman, University of Texas Press, 134 pages , 1969 .

[16]  Christer Halldin,et al.  Saturation analysis of specific 11C Ro 15‐1788 binding to the human neocortex using positron emission tomography , 1989 .

[17]  T. Crow,et al.  [3H]R05-4864 and [3H]flunitrazepam binding in kainate-lesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type , 1983, Brain Research.

[18]  R. Naquet,et al.  Central type benzodiazepine binding sites: A positron emission tomography study in the baboon's brain , 1984, Neuroscience Letters.

[19]  R. Naquet,et al.  Status epilepticus induced by pentylenetetrazole modulates in vivo [11C]Ro 15-1788 binding to benzodiazepine receptors. Effects of ligands acting at the supramolecular receptor complex. , 1988, European journal of pharmacology.

[20]  M. Zell,et al.  Highly sensitive assay of benzodiazepine antagonist in plasma by capillary gas chromatography with nitrogen-selective detection. , 1986, Journal of chromatography.

[21]  C. D. Arnett,et al.  The utility of 1-[18F]fluoro-3-iodopropane for the synthesis of certain dopamine D-1 and benzodiazepine receptor radioligands. , 1990, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[22]  Non-steady-state measurement of in vivo receptor binding with positron emission tomography: "dose-response" analysis , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  M E Raichle,et al.  Brain Blood Volume, Flow, and Oxygen Utilization Measured with 15O Radiotracers and Positron Emission Tomography: Revised Metabolic Computations , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  P. Griffiths,et al.  Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease , 1990, Journal of the Neurological Sciences.

[25]  L. Eriksson,et al.  Imaging of [11C]-labelled Ro 15-1788 binding to benzodiazepine receptors in the human brain by positron emission tomography. , 1985, Journal of psychiatric research.

[26]  E. Brouillet,et al.  Interaction of suriclone with central type benzodiazepine receptors in living baboons. , 1990, European journal of pharmacology.

[27]  G. Sedvall,et al.  Cerebral uptake of 11C—Ro 15—1788 and its acid metabolite 11C—Ro 15—3890; PET study in healthy volunteers , 1989 .

[28]  R. Naquet,et al.  Benzodiazepine receptors studied in living primates by positron emission tomography: antagonist interactions. , 1987, European journal of pharmacology.

[29]  M. Manchon,et al.  Benzodiazepine receptor and neurotransmitter studies in the brain of suicides. , 1987, Life sciences.

[30]  M. Mintun,et al.  A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography , 1984, Annals of neurology.