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Saturation analysis of specific 11 C Ro 15‐1788 binding to the human neocortex using positron emission tomography
Author(s) -
Persson Anders,
Pauli Stefan,
Halldin Christer,
StoneElander Sharon,
Farde Lars,
Sjögren Irene,
Sedvall Göran
Publication year - 1989
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.470040105
Subject(s) - flumazenil , neocortex , benzodiazepine , chemistry , positron emission tomography , population , antagonist , receptor , human brain , endocrinology , medicine , pharmacology , nuclear medicine , neuroscience , psychology , biochemistry , environmental health
The 11 C‐labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand‐reduced 11 C‐flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor‐poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density ( B max ) and equilibrium dissociation constant ( K d ) values on the basis of certain assumptions B max values were in the order of 90 pmol/g and K d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that 11 C‐flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.