First human evidence of d-amphetamine induced displacement of a D2/3 agonist radioligand: A [11C]-(+)-PHNO positron emission tomography study

Neuropsychopharmacology. 2008 Jan;33(2):279-89. doi: 10.1038/sj.npp.1301400. Epub 2007 Apr 4.


Imaging the competition between D(2/3) radioligands and endogenous dopamine is so far the only way to measure dopamine release in the living human brain. The dopamine D(2) receptor exists in a high (D(2)(high)) and a low-affinity state for dopamine. Under physiological conditions, dopamine is expected to bind to D(2)(high) only. [(11)C]-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is the first D(2/3) agonist radioligand for positron emission tomography (PET) imaging in humans. Since [(11)C]-(+)-PHNO is expected to bind preferentially to D(2)(high), it should be particularly vulnerable to competition with endogenous dopamine. Nine healthy subjects participated in two PET scans, one after administration of d-amphetamine and one after placebo. [(11)C]-(+)-PHNO PET test re-test variability was determined in 11 healthy subjects. Binding potentials (BPs) were calculated for caudate, putamen, ventral striatum, and globus pallidus. d-Amphetamine led to a significant decrease of [(11)C]-(+)-PHNO BPs in caudate (-13.2%), putamen (-20.8%), and ventral striatum (-24.9%), but not in globus pallidus (-6.5%). d-Amphetamine-induced displacement correlated with serum d-amphetamine levels in all regions but caudate. This is the first report on competition between endogenous dopamine and a D(2/3) agonist radioligand in humans. [(11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dextroamphetamine / pharmacology*
  • Dopamine Agonists / chemical synthesis
  • Female
  • Globus Pallidus / diagnostic imaging
  • Globus Pallidus / metabolism
  • Humans
  • Male
  • Oxazines / chemical synthesis*
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / metabolism


  • Dopamine Agonists
  • Oxazines
  • naxagolide
  • Dextroamphetamine