Substituted Benzamides as Ligands for Visualization of Dopamine Receptor Binding in the Human Brain by Positron Emission Tomography

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 11; pp. 3863 - 3867
• Main Authors: Farde, Lars, Ehrin, Erling, Eriksson, Lars, Greitz, Torgny, Hall, Hakan, Hedstrom, Carl-Goran, Litton, Jan-Erik, Sedvall, Goran
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.06.1985; National Acad Sciences
• Subjects: Animals; Antipsychotic agents; Benzamides; Benzamides - metabolism; Biological and medical sciences; Blood; Brain - metabolism; Cell physiology; Cerebellum; Dopamine receptors; Fundamental and applied biological sciences. Psychology; Haloperidol - metabolism; Humans; Inhibitory concentration 50; Kinetics; Ligands; Macaca fascicularis; Molecular and cellular biology; Neurotransmission; Positron emission tomography; Raclopride; Radioactive decay; Receptors; Receptors, Dopamine - metabolism; Species Specificity; Tissue Distribution; Tomography, Emission-Computed - methods; Human; Visualization; Ligand; Neuroleptic; Brain(Invertebrata); Schizophrenia; Molecular interaction; Mechanism of action; Positron emission tomography; Dopaminergic receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.11.3863

Two substituted benzamides, FLB 524 and raclopride, were labeled with11C 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.