A feasibility study of [11C]SA4503-PET for evaluating sigmal receptor occupancy by neuroleptics: the binding of haloperidol to sigma1 and dopamine D2-like receptors

Ann Nucl Med. 2006 Oct;20(8):569-73. doi: 10.1007/BF03026824.

Abstract

We investigated feasibility of positron emission tomography (PET) with [11C]SA4503 for evaluating the sigma1 receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D2-like receptor (D2R) as well as to be a representative non-selective antagonist for sigma1 receptor (sigma1R), was selected as a model drug. Three healthy male subjects underwent 60-min [11C]raclopride-PET and 90-min [11C]SA4503-PET scans successively at a 120-min interval twice in a day for baseline measurement and on another day for haloperidol-loading measurement 16 hours after peroral administration of 3 mg of haloperidol. Binding potential (BP) of [11C]raclopride and [11C]SA4503 was quantitatively evaluated and the sigma1R and D2R occupancy rates were determined. D2R occupancy rates by haloperidol were 64% and 62% in the caudate and putamen, respectively, 16 h after the administration, while sigma1R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the sigma1R receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [11C]SA4503-PET can be used for evaluating the sigma1R occupancy rates by neuroleptics or other drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology*
  • Brain / pathology
  • Dopamine Antagonists / pharmacology*
  • Feasibility Studies
  • Haloperidol / pharmacology*
  • Humans
  • Male
  • Nootropic Agents / pharmacology*
  • Piperazines / pharmacology*
  • Positron-Emission Tomography / instrumentation*
  • Positron-Emission Tomography / methods
  • Protein Binding
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, sigma / metabolism*
  • Time Factors

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Nootropic Agents
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, sigma
  • SA 4503
  • Haloperidol