title: Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography.
abstract: Two substituted benzamides, FLB 524 and raclopride, were labeled with 11C and examined for their possible use as ligands for positron emission tomography (PET)-scan studies on dopamine-2 (D-2) receptors in the brains of monkeys and healthy human subjects. Both ligands allowed the in vivo visualization of D-2 receptor binding in the corpus striatum caudate nucleus/putamen complex in PET-scan images. [11C]Raclopride showed a high ratio of specific striatal to nonspecific cerebellar binding, and the kinetics of binding of this ligand made it optimal for PET studies. The in vivo binding of [11C]raclopride in the striatum of cynomolgus monkeys was markedly reduced by displacement with haloperidol. This and previous in vitro data indicate that [11C]raclopride binds selectively to striatal D-2 dopamine receptors. In healthy human subjects, [11C]raclopride binding in the caudate nucleus/putamen was 4- to 5-fold greater than nonspecific binding in the cerebellum. In comparison with previously available ligands for PET-scan studies on central dopamine receptors in man, [11C]raclopride appears to be advantageous with regard to (i) specificity of binding to D-2 receptors, (ii) the high ratio between binding in dopamine-rich (caudate, putamen) and dopamine-poor (cerebellum) human brain regions, and (iii) rapid association and reversibility of specific binding. [11C]Raclopride should be a valuable tool for characterizing D-2 receptors in the brains of patients with neuropsychiatric disorders.
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008252:Macaca fascicularis; D020891:Raclopride; D011954:Receptors, Dopamine / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D001549:Benzamides; D011954:Receptors, Dopamine; D020891:Raclopride; C045658:FLB 524; D006220:Haloperidol