The metabolism of iodine-123 labelled 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine (NNC 13-8241) measured in human plasma is only minor

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The imidazobenzodiazepine derivate 123I-labelled 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]-benzodiazepine (NNC 13–8241) is a partial benzodiazepine agonist and binds with a high affinity to the benzodiazepine receptor. The favourable kinetic properties indicate that [123I]NNC 13–8241 is a promising SPET ligand. In the present study, an extensive examination of the metabolite pattern of [123I]NNC 13–8241 in plasma and urine from seven healthy subjects was performed using gradient HPLC. After injection of [123I]NNC 13–8241 into human beings, only one radioactive metabolite was found in plasma 3–300 min post injection. This polar metabolite eluted together with the solvent front fraction. The proportion of unchanged [123I]NNC 13–8241 was 82–86 per cent during the entire study. In addition, two other radioactive metabolites were found in urine. The first metabolite was lipophilic and eluted slightly before the parent compound [123I]NNC 13–8241. The second metabolite eluted slightly after solvent front peak. The amount of unchanged [123I]NNC 13–8241 in human urine was 9 per cent and the solvent front fraction contained 72 per cent of total radioactivity. No detectable radioactivity appeared with the same retention time as synthetisized nor-NNC 13–8241 in plasma or urine, which excludes the possibility of in vivo demethylation of [123I]NNC 13–8241. In conclusion, the [123I]NNC 13–8241 was found to have only a minor metabolism, which favours its use as a SPET tracer for quantitation of the benzodiazepine receptor. © 1998 John Wiley & Sons, Ltd.