C-11-LABELED AND BR-76-LABELED NNC-22-0010, SELECTIVE DOPAMINE D-1 RECEPTOR RADIOLIGANDS FOR PET

NNC 22-0010 is a new dopamine antagonist with a high affinity and sele ctivity for D-1 receptors in vitro. NNC 22-0010 has both an N methyl g roup and a bromine, which allows radiolabelling with either C-11 or Br -76. We labelled [C-11]NNC 22-0010 by N methylation of the free base o f the secondary amine with [C-11]methyl iodide in a total radiochemica l yield of 40%. The total synthesis time was 30 min. The specific radi oactivity at time of injection of the radioligand was 48 to 55 GBq/mu mol. The [Br-76]NNC 22-0010 was synthesized from the iodine precursor by an exchange reaction with Br-76 using a Cu+-assisted nucleophilic s ubstitution reaction. The radiochemical yield was 60% after purificati on. Specific radioactivity at time of injection of the radioligand was 6 to 20 GBq/mu mol. In PET experiments with [C-11]NNC 22-0010 and [Br -76]NNC 22-0010 there was a rapid uptake of radioactivity in the monke y brain. The striatum to cerebellum ratio was 2-2.5 after 1 h. Binding in the striatum was displaced by SCH 23390, whereas binding in the ce rebellum was not reduced. Metabolite studies showed that 1 h after inj ection about 20% of the radioactivity in plasma represented unchanged radioligand. This value was on the same level for at least 6 h. The re sults indicate that radiolabelled NNC 22-0010 has potential for imagin g dopamine D-1 receptors selectively in the human brain.