[125I](±)FISCH: A new CNS D-1 dopamine receptor imaging ligand

Abstract Radiolabeling and in vitro and in vivo evaluation of an iodinated benzazepine: [ 125 I] FISCH 7-Chloro-8-hydroxy-1-(4′-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, as a potential imaging agent for CNS D-1 dopamine receptors in animals, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats (2.70, 1.28, 0.48 %dose/whole brain at 2, 15 and 60 min, respectively). The striatum/cerebellum ratio was 2.50 at 60 min after the injection. The regional distribution in rat brain, as measured by ex vivo autoradiography, displayed highest uptake in the regions of the striatal complex and the substantia nigra, regions known to have a high concentration of D-1 dopamine receptors. Furthermore, this localized regional cerebral distribution was blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist. The in vitro binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 ± 0.15 nM. Competition data ( in vitro ) showed the following rank order of potency: SCH-23390 > (±)IBZP ⪢ apomorphine > 4101 ketanserin ∼ spiperone. The preliminary data suggest that this analog of SCH-23390 shows similar selectivity for the CNS D-1 receptor.