Kinetics and displacement of [11C]RO 15-1788, a benzodiazepine antagonist, studied in human brain in vivo by positron tomography.
The brain regional distribution and kinetics of RO 15-1788, a benzodiazepine (BZD) antagonist labeled with 11C was studied by time-of-flight positron tomography after intravenous injection in four normal human volunteers. In two control studies, there was a high uptake of [11C]RO 15-1788 in gray matter structures initially (brain/blood ratio approximately 3), and subsequent retention that was highest in cerebral cortex, a structure known to have a high density of BZD receptors in vitro. Variation in tissue kinetics of [11C]RO among different gray matter structures may, however, suggest regional differences in binding characteristics or environment of BZD receptors. In two displacement studies, unlabeled RO 15-1788 was injected ten minutes after the radioligand: there was an immediate and marked washout of [11C]brain radioactivity that reached 70% in the occipital cortex with a 0.05 mg/kg dose (indicating a high specific to non-specific binding ratio) but was less prominent with a 0.01 mg/kg dose. These data suggest that [11C]RO 15-1788 may be useful for in vivo mapping of human brain BZD receptors using positron tomography.
Samson
Y
Y
Hantraye
P
P
Baron
J C
JC
Soussaline
F
F
Comar
D
D
Mazière
M
M
D000328:Adult; D001570:Benzodiazepinones / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003292:Convulsants / Q000097:blood / Q000378:metabolism*; D005260:Female; D005442:Flumazenil; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001570:Benzodiazepinones; D003292:Convulsants; D011963:Receptors, GABA-A; D005442:Flumazenil