Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide

Abstract

In developing central nervous system (CNS) dopamine D-2 receptor imaging agents, enantiomers, R-(+) and S-(-) isomers, of 3-[125I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide, [125I]IBZM, were synthesized, and their in vitro binding characteristics were evaluated in rat striatum tissue preparation. The (S)-(-)-[125I]IBZM showed high specific dopamine D-2 receptor binding (Kd = 0.43 nM, Bmax = 0.48 pmol/mg of protein), Competition data of various ligands for IBZM binding displayed the following rank order of potency: spiperone > (S)-(-)-IBZM > (+)-butaclamol .mchgt. (R)-(+)-IBZM > (S)-(-)-BZM > dopamine > ketanserin > SCH23390 .mchgt. propanolol. The results indicate that [125I]IBZM binds specifically to the dopamine D-2 receptor with stereospecificity. The [125I]IBZM is potentially useful as an imaging agent for the investigation of dopamine D-2 receptor with stereospecificity. The [125I]IBZM is potentially useful as an imaging agent for the investigation of dopamine D-2 receptors in humans.