In vivo quantification of regional dopamine-D3 receptor binding potential of (+)-PHNO: Studies in non-human primates and transgenic mice

Synapse. 2009 Sep;63(9):782-93. doi: 10.1002/syn.20658.


Examination of dopamine-D3 (D3) receptors with positron emission tomography (PET) have been hampered in the past by the lack of a PET ligand with sufficient selectivity for D3 over dopamine-D2 (D2) receptors. The two types co-localize in the brain, with D2 density significantly higher than D3, hence nonselective PET ligands inform on D2, rather than D3 status. [(11)C]-(+)-PHNO is a novel PET ligand with a preferential affinity for D3 over D2. We used the selective D3 antagonist, SB-277011 to dissect regional fractions of the [(11)C]-(+)-PHNO signal attributable to D3 and D2 in primate brain. The results were compared with quantitative autoradiography with (3)H-(+)-PHNO in wild-type, D2-knock-out, and D3-knock-out mice examined at baseline and following administration of SB-277011. Both sets of results converged to indicate a predominant D3-related component to (+)-PHNO binding in extra-striatal regions, with binding in the midbrain being entirely attributable to D3. The midbrain is thus an excellent target region to examine D3 receptor occupancy with [(11)C]-(+)-PHNO PET in vivo.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Brain / anatomy & histology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Dopamine / metabolism*
  • Dopamine Agonists / metabolism*
  • Dopamine Antagonists / metabolism
  • Mesencephalon / anatomy & histology
  • Mesencephalon / diagnostic imaging
  • Mesencephalon / metabolism
  • Mice
  • Mice, Knockout
  • Nitriles / metabolism
  • Oxazines / metabolism*
  • Papio anubis
  • Positron-Emission Tomography
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / drug effects
  • Receptors, Dopamine D3 / genetics
  • Receptors, Dopamine D3 / metabolism*
  • Tetrahydroisoquinolines / metabolism


  • Dopamine Agonists
  • Dopamine Antagonists
  • Nitriles
  • Oxazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • SB 277011
  • Tetrahydroisoquinolines
  • naxagolide
  • Dopamine