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.