Biological properties of 2'-[18F]fluoroflumazenil for central benzodiazepine receptor imaging.
A novel positron emitting agent, 2'-[18F]fluoroflumazenil (fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate, FFMZ), has been reported for benzodiazepine imaging. In the present study, biological properties of [18F]FFMZ were investigated. Stability tests of [18F]FFMZ in human and rat sera were performed. Biodistribution was investigated in mice and phosphorimages of brains were obtained from rats. A receptor binding assay was performed using rat brain (mixture of cortex and cerebellum) homogenate. A static positron emission tomography (PET) image was obtained from a normal human volunteer. Although [18F]FFMZ was stable in human serum, it was rapidly hydrolyzed in rat serum. The hydrolysis was 39%, 63% and 92% at 10, 30 and 60 min, respectively. According to the biodistribution study in mice, somewhat even distribution (between 2 approximately 3% ID/g) was observed in most organs. Intestinal uptake increased up to 6% ID/g at 1 h due to biliary excretion. Bone uptake slowly increased from 1.5% to 3.5% ID/g at 1 h. High uptakes in the cortex, thalamus and cerebellum, which could be completely blocked by coinjection of cold FMZ, were observed by phosphorimaging study using rats. Determination of Kd value and Bmax using rat brain tissue was performed by Scatchard plotting and found 1.45+/-0.26 nM and 1.08+/-0.03 pmol/mg protein, respectively. The PET image of the normal human volunteer showed high uptake in the following decreasing order: frontal cortex, temporal cortex, occipital cortex, cerebellum, parietal cortex and thalamus. In conclusion, the new FMZ derivative, [18F]FFMZ appears to be a promising PET agent for central benzodiazepine receptor imaging with a convenient labeling procedure and a specific binding property.
Chang
Young Soo
YS
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea.
Jeong
Jae Min
JM
Yoon
Young Hyun
YH
Kang
Won Jun
WJ
Lee
Seung Jin
SJ
Lee
Dong Soo
DS
Chung
June-Key
JK
Lee
Myung Chul
MC
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
C483765:2'-fluoroflumazenil; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D005442:Flumazenil