Biodistribution, binding specificity and metabolism of [18F]fluoroethylflumazenil in rodents.
Pre-clinical studies were carried out in order to characterize in rodents the biodistribution, the binding specificity and the metabolism of [18F]Fluoroethylflumazenil ([18F]FEF), a potential candidate for in vivo imaging of the benzodiazepine receptors. In vivo competition with flumazenil indicates that [18F]FEF binds specifically to the benzodiazepine receptor in the brain. The accumulation of [18F]FEF was significantly lower than using [3H]Flumazenil. The rather low accumulation in the brain is due to a rapid metabolism of [18F]FEF in hydrophylic metabolites which cannot cross the blood brain barrier, and are rapidly eliminated in the urine. Inhibition of the metabolism by acetaminophen (chemically induced hepatitis) led to a significant increase of the radioactivity found in the circulating blood and in the brain, while these results were not observed using classical inhibitors of the cytochrome CYP450, cimetidine and ketoconazole.
Levêque
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P
Unité de chimie pharmaceutique et de radiopharmacie, Université catholique de Louvain, Avenue Mounier 73.40 B-1200, Brussels, Belgium.
Labar
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D
Gallez
B
B
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005442:Flumazenil / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
C444361:5-(2'-fluoroethylflumazenil); D019275:Radiopharmaceuticals; D005442:Flumazenil