RADIOIODINATED 2'-IODODIAZEPAM - A POTENTIAL IMAGING AGENT FOR SPECT INVESTIGATIONS OF BENZODIAZEPINE RECEPTORS

2'-Iododiazepam (2'-IDZ) is the diazepam analogue iodinated at the 2'- position of C-5 phenyl ring which was synthesized and evaluated as a p otential radiopharmaceutical for investigating brain benzodiazepine re ceptors by SPECT. The I-125-2'-iododiazepam was synthesized by halogen exchange reaction and purified by HPLC. In vitro competitive binding studies With H-3-diazepam, using rat cortical synaptosomal membranes, showed that the affinity of 2'-IDZ for benzodiazepam receptors was hig her than that in diazepam and flumazenil (RO15-1788). Biodistribution studies in mice showed that the brain uptake of 2'-iododiazepam was ra pid and profound, and in the brain higher accumulation was found in th e cortex than in other regions. Furthermore, the cortical uptake was d isplaced by benzodiazepinergic compounds. In vivo uptake was assessed by autoradiographic studies. Thus, 2'-iododiazepam bound to benzodiaze pine receptors in vivo and therefore holds great potential for in vivo benzodiazepine receptor studies.