SYNTHESIS AND IN-VITRO AND IN-VIVO CHARACTERISTICS OF AN IODINATED ANALOG OF THE BETA-ADRENOCEPTOR ANTAGONIST CARAZOLOL

A new (radio)iodinated, beta-adrenoceptor ligand, o-(2E)-propenyl)-ami no]-2-hydroxypropoxy]carbazole (CYBL8E, 1), was prepared. 1 is an iodi nated analogue of the high-affinity beta-adrenoceptor antagonist caraz olol (2). The asymmetric synthesis was achieved in four steps starting from 4-hydroxycarbazole. The iodine-123-labeled form was obtained by an iododestannylation reaction with [I-123]NaI in the presence of H2O2 . Using classical in vitro displacement experiments with membrane frac tions of cardiac left ventricular muscle, 1 proved to have a high affi nity for the receptor (K-i = 0.31 +/- 0.03). Biodistribution studies p erformed in New Zealand white rabbits demonstrated the specificity of the binding in vivo to the receptor. Uptake of [I-123]1 was reduced si gnificantly in both atrial muscle, left ventricular muscle, frontal co rtex, cerebellum, and striatum, by the pretreatment of the animals wit h different beta-adrenoceptor antagonists. In conclusion, 1 is a poten t nonselective beta-adrenoceptor antagonist, which binds specifically to the beta-adrenoceptor in vivo, and is therefore a promising radioli gand for the imaging of beta-adrenoceptors using single photon emissio n computerized tomography.