Different sensitivities to competitive inhibition of benzodiazepine receptor binding of 11C-iomazenil and 11C-flumazenil in rhesus monkey brain.
The in vivo binding kinetics of 11C-iomazenil were compared with those of 11C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either 11C-iomazenil or 11C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 microg/kg). The regional distribution of 11C-iomazenil in the brain was similar to that of 11C-flumazenil, but the sensitivity of 11C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of 11C-flumazenil binding. A significant reduction in 11C-flumazenil binding in the cerebral cortex was observed with 20 microg/kg of flumazenil, whereas a relatively smaller inhibition of 11C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that 11C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain.
Inoue
O
O
School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Japan. inoue@sahs.med.osaka-u.ac.jp
Hosoi
R
R
Kobayashi
K
K
Itoh
T
T
Gee
A
A
Suzuki
K
K
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D007700:Kinetics; D008253:Macaca mulatta; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D058787:GABA-A Receptor Antagonists; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil