Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity.

Research output: Contribution to journalJournal articleResearchpeer-review

  • D F Wong
  • Gjedde, Albert
  • H N Wagner
  • R F Dannals
  • K H Douglass
  • J M Links
  • M J Kuhar
A method for estimating receptor density (Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3-N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g-1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 nM by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.
Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Volume6
Issue number2
Pages (from-to)147-53
Number of pages6
ISSN0271-678X
Publication statusPublished - 1986
Externally publishedYes

ID: 14946193