TY - JOUR
T1 - Binding of 5-(2′-[18F]fluoroenthyl)flumazenil to central benzodiazepine receptors measured in living baboon by positron emission tomography
AU - Moerlein, Stephen M.
AU - Perlmutter, Joel S.
N1 - Funding Information:
We arc grateful to I. Lich and J. Karl for expert technical assistance with the animal studies. J. Hood for data processing, W. Margenau and J. Robison for radioisotope production, and T. Duck-eft fl)r manuscript preparation. Wc also thank Hoffman-La Roche Laboratories for kindly providing flumazenil and nor-flumazenil for this research, and Dr. D. Parkinson for performing in vitro binding assays. Tbis work was supported by the McDonnell (?enter for the Study of Higher Brain Function, NIH FIRST Award IR29N526788 (SMM), NIIt Grants HLI3851, AGG()8377, RR04865 as well as the generous support of the Greater St. Louis C'hapter of the American Parkinson's Disease Association.
PY - 1992/7/21
Y1 - 1992/7/21
N2 - 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.
AB - 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.
KW - Benzodiazepine receptors
KW - Flumazenil
KW - Imaging
KW - Neuroreceptors
KW - PET (positron emission tomography)
KW - [F]FEF (5-(2′-[F]Fluoroethyl)flumazenil)
UR - http://www.scopus.com/inward/record.url?scp=0026653451&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(92)90153-U
DO - 10.1016/0014-2999(92)90153-U
M3 - Article
C2 - 1327820
AN - SCOPUS:0026653451
SN - 0014-2999
VL - 218
SP - 109
EP - 115
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -