SPECT IMAGING OF THE BENZODIAZEPINE RECEPTOR IN NONHUMAN PRIMATE BRAIN WITH [I-123] RO 16-0154

We have used SPECT (single photon emission computed tomography) imaging in non-human primates to examine the time course and pharmacological specificity of I-123-labeled Ro 16-0154 as an in vivo probe of the benzodiazepine receptor. Maximal brain uptake was reached approximately 70 min post i.v. administration of the radioligand and represented approximately 10% of the injected dose. The regional distribution of radioactive densities was consistent with the known distribution of benzodiazepine receptors in primate brain, with highest uptake localized over the occipital area. Washout of radioactivity was relatively slow with a rate of 3% per hour after the time of peak radioactivity. Injection of the benzodiazepine antagonist Ro 15-1788 (0.2-0.3 mg/kg i.v.) caused a rapid decrease of more than 90% of radioactivity from brain. In summary, [I-123]Ro 16-0154 is a promising in vivo SPECT radioligand for the benzodiazepine receptor, with high brain uptake, a stable period of peak radioactivity, appropriate regional distribution, and ability to be displaced by other benzodiazepine receptor agents.