Quantification of neuroreceptors in the living human brain: III. D2- like dopamine receptors: Theory, validation, and changes during normal aging

Dean F. Wong, David Young, P. David Wilson, Carolyn Cidis Meltzer, Albert Gjedde

Research output: Contribution to journalArticlepeer-review

Abstract

Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D2-1ike receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D2-like dopamine receptor density in the human brain with an occupying ligand (unlabeled haloperidol) and a radioligand (labeled 3-N-methylspiperone). The method was examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the representation of tracer metabolism by high-pressure liquid chromatography and model assays, calculation of the lumped constant D(w) from the value of its components, and comparable tracer partition coefficients in vitro and in vivo. In error analysis, the method consistently performed as well as the direct least-squares regression at statistical noise levels appropriate for the tomograph used in these studies. The method revealed that the density of the D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.

Original languageEnglish (US)
Pages (from-to)316-330
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number3
DOIs
StatePublished - Mar 1997

Keywords

  • Dopamine receptors
  • Positron emission tomography
  • Receptor quantification
  • Schizophrenia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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