Affinity and selectivity of [¹¹C]-(+)-PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo

Synapse. 2012 Jun;66(6):489-500. doi: 10.1002/syn.21535. Epub 2012 Feb 24.


Although [¹¹C]-(+)-PHNO has enabled quantification of the dopamine-D3 receptor (D3R) in the human brain in vivo, its selectivity for the D3R is not sufficiently high to allow us to disregard its binding to the dopamine-D2 receptor (D2R). We quantified the affinity of [¹¹C]-(+)-PHNO for the D2R and D3R in the living primate brain. Two rhesus monkeys were examined on four occasions each, with [¹¹C]-(+)-PHNO administered in a bolus + infusion paradigm. Varying doses of unlabeled (+)-PHNO were coadministered on each occasion (total doses ranging from 0.09 to 5.61 μg kg⁻¹). The regional binding potential (BP(ND) ) and the corresponding doses of injected (+)-PHNO were used as inputs in a model that quantified the affinity of (+)-PHNO for the D2R and D3R, as well as the regional fractions of the [¹¹C]-(+)-PHNO signal attributable to D3R binding. (+)-PHNO in vivo affinity for the D3R (K(d)/f(ND) ~0.23-0.56 nM) was 25- to 48-fold higher than that for the D2R (K(d)/f(ND) ~11-14 nM). The tracer limits for (+)-PHNO (dose associated with D3R occupancy ~10%) were estimated at ~0.02-0.04 μg kg⁻¹ injected mass for anesthetized primate and at 0.01-0.02 μg kg⁻¹ for awake human positron emission tomography (PET) studies. Our data enabled a rational design and interpretation of future PET studies with [¹¹C]-(+)-PHNO.

MeSH terms

  • Animals
  • Benzoxazines / chemistry
  • Benzoxazines / metabolism*
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes / chemistry
  • Dopamine Agonists / metabolism*
  • Female
  • Macaca mulatta / metabolism
  • Naphthols / chemistry
  • Naphthols / metabolism*
  • Oxazines / metabolism*
  • Positron-Emission Tomography
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Substrate Specificity


  • 4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho(1,2-b)(1,4)oxazin-9-ol
  • Benzoxazines
  • Carbon Radioisotopes
  • Dopamine Agonists
  • Naphthols
  • Oxazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • naxagolide