PET analysis of [11C]flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls.
Benzodiazepine (BZ) receptor binding in the brain was determined in five chronic alcohol-dependent men and in five healthy male control subjects using [11C]flumazenil (Ro 15-1788) and positron emission tomography (PET). Magnetic resonance imaging was used to evaluate brain anatomy and pathology, and to define regions of interest in the brain. [11C]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400-3400 Ci/mmol) and the second with low (approximately 1 Ci/mmol) specific radioactivity. Radioactivity in the pons was taken as an estimate of free and nonspecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dCb(t)/dt) was equal to zero. The values were used in a Scatchard analysis for determination of the maximum density of binding sites (Bmax) and the equilibrium binding constant (Kd). The mean values of Bmax and Kd were about the same in the two groups, but the Bmax variance for the alcoholics was significantly greater for all regions of interest as compared with the healthy volunteers. The results may indicate that chronic alcohol consumption has multiple effects on the BZ receptor complex.
Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden.
J E
JE
Litton
J
J
Neiman
S
S
Pauli
L
L
Farde
T
T
Hindmarsh
C
C
Halldin
G
G
Sedvall
D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D005442:Flumazenil / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil