RADIOIODINATED NORDIAZEPAM ANALOG FOR IN-VIVO ASSESSMENT OF BENZODIAZEPINE RECEPTORS BY SINGLE-PHOTON EMISSION TOMOGRAPHY

2'-Iodo-nordiazepam (2'-IND), a nordiazepam analog iodinated at the 2' -position of the C-5 phenyl ring, was synthesized and evaluated as a p otential radiopharmaceutical for investigating brain benzodiazepine re ceptors by SPECT. [I-125]2'-IND was synthesized by the halogen exchang e reaction and purified by HPLC. In an in vitro competitive binding st udy using [H-3]diazepam and rat cortical synaptosomal membranes, 2'-IN D showed an almost equal affinity for benzodiazepine receptors as diaz epam. In a saturation binding study using rat cortical synaptosomal me mbranes, 2'-IND displayed a K-d of 1.10 nM and a B-max of 1.87 pmol/mg protein. Biodistribution and metabolism studies in mice showed that [ I-125]2'-IND exhibited rapid and high accumulation in the brain, and t hat the cerebral uptake and distribution of this compound occurred in the intact form. Furthermore, the administration of diazepam and fluma zenil reduced cortical uptake by approx. 20%, suggesting that the upta ke of 2'-IND occurred at least partly in association with benzodiazepi ne receptors.