In vitro and In vivo Evaluation of [123I]IBZM: A Potential CNS D-2 Dopamine Receptor Imaging Agent

In vitro binding characteristics of a CNS dopamine D-2 receptor imaging agent, (S)-N-((1-ethyl-2-pyrrolidinyl)) methyl-2-hydroxy-3-iodo-6-methoxybenzamide ((/sup 125/I)IBZM), was carried out in rats. Also brain images, as well as organ biodistribution were determined in a monkey following the administration of /sup 123/I-labeled compound. The S-(-)-I(/sup 125/I)IBZM showed high specific dopamine D-2 receptor binding in rat striatum (Kd = 0.426 +/- 0.082 nM, Bmax = 480 +/- 22 fmol/mg of protein). Competition of various ligands for the IBZM binding displayed the following rank order of potency: spiperone greater than S(-)IBZM much greater than R(+)IBZM greater than or equal to S(-)BZM greater than dopamine greater than ketanserin greater than SCH-23390 much greater than propranolol, norepinephrine, serotonin. In vivo planar images of a monkey injected with (/sup 123/I)IBZM demonstrated a high concentration in basal ganglia of brain. The ratios of activity in the basal ganglia to cerebellum and the cortex to cerebellum in monkey brain were 4.93 and 1.44, respectively, at 120 min postinjection. These preliminary results indicate that (/sup 123/I)IBZM is a potentially promising imaging agent for the investigation of dopamine D-2 receptors in humans.