INITIAL HUMAN STUDIES WITH SINGLE-PHOTON EMISSION TOMOGRAPHY USING I-123 LABELED METHYL-6-OXO-4H-IMIDAZO[1,5-A][1,4]-BENZODIAZEPINE (NNC-13-8241)

The iodine-123 labelled ligand methyl-6-oxo-4H-imidazo[1,5-a][1,4]-ben zodiazepine ([I-123]NNC 13-8241) was evaluated as a probe for in vivo imaging of benzodiazepine receptor sites in The human brain. Four heal thy volunteers were imaged with a high-resolution single-photon emissi on tomography (SPET) scanner. The metabolism of [I-123]NNC 13-8241 in plasma was slow. The total brain uptake was about 1.5-fold higher than that of [I-123]iomazenil. The specific binding in the cortical areas was high and less intense in tile thalamus. The most intense uptake wa s seen in the occipital cortex, The peak cortical uptake of [I-123]NNC 13-8241 was observed 6-10 h after the injection of tracer. The radiat ion burden to the patient was moderate, being 2.5 . 10(-2) mSv/MBq (ef fective dose equivalent). A slow metabolism together with favourable k inetics indicates that [I-123]NNC 13-8241 is a specific and promising SPET ligand for imaging benzodiazepine receptor sites in the living hu man brain.