(.+-.)-7-Chloro-8-hydroxy-1-(4'-[125I]iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine: a potential CNS D-1 dopamine receptor imaging agent

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Abstract
Synthesis, radiolabeling, and in vitro and in vivo properties of an iodinated benzazepine, (.+-.)-7-chloro-8-hydroxy-1-(4''-[125I]iodophenyl-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, [125I]FISCH, as a potential imaging agent for evaluation of central nervous system (CNS) D-1 dopamine receptors in humans, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats (2.27, 1.40, 0.55 % dose/whole brain at 2, 15, and 60 min, respectively). The striatum/cerebellum ratio was high (2.47 at 60 min after the injection). The 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 > (.+-.)-FISCH > (.+-.)-IBZP .mchgt. apomorphine > WB 4010 > ketanserin .apprxeq. spiperone. The preliminary data suggest that the agent is highly selective for the CNS D-1 receptor.