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

Article abstract of DOI:10.1021/jm00400a027

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]d 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 (K(d) = 0.43 nM, B(max) = 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 >> (R)-(+)-IBZM > (S)-(-)-BZM > dopamine > ketanserin > SCH23390 >> propranolol. The results indicate that [¹²⁵I]IBZM binds specifically to the dopamine D-2 receptor with stereospecificity. The [¹²³I][IBZM is potentially useful as an imaging agent for the investigation of dopamine D-2 receptors in humans.