The metabolism of iodine-123 labelled 3-(5-cyclopropyl-1,2,4-oxadiazo- 3-y1)-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

The imidazobenzodiazepine derivate ¹²³I-labelled 3-(5-cyclopropyl- 1,2,4-oxadiazo-3-y1)-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.