Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography

Proc Natl Acad Sci U S A. 1985 Jun;82(11):3863-7. doi: 10.1073/pnas.82.11.3863.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / metabolism*
  • Brain / metabolism*
  • Haloperidol / metabolism
  • Humans
  • Kinetics
  • Macaca fascicularis
  • Raclopride
  • Receptors, Dopamine / metabolism*
  • Species Specificity
  • Tissue Distribution
  • Tomography, Emission-Computed / methods*

Substances

  • Benzamides
  • Receptors, Dopamine
  • Raclopride
  • FLB 524
  • Haloperidol