title: 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 greater than (S)-(-)-IBZM greater than (+)-butaclamol much greater than (R)-(+)-IBZM greater than (S)-(-)-BZM greater than dopamine greater than ketanserin greater than SCH23390 much greater than propanolol. 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.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia 19104.
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: R
authors.initials: R
authors.lastname: Kasliwal
authors.forename: S G
authors.initials: SG
authors.lastname: Pan
authors.forename: M P
authors.initials: MP
authors.lastname: Kung
authors.forename: R H
authors.initials: RH
authors.lastname: Mach
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Guo
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide