[11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography

Life Sci. 1996;58(10):PL 187-92. doi: 10.1016/0024-3205(96)00013-6.

Abstract

The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occurred within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [11C]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [11C]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / ultrastructure
  • Carbon Radioisotopes
  • Chromatography, High Pressure Liquid
  • Fluorobenzenes / chemical synthesis*
  • Fluorobenzenes / metabolism*
  • Fluorobenzenes / pharmacokinetics
  • Hydrocarbons, Iodinated / chemistry
  • Isotope Labeling / methods
  • Macaca fascicularis
  • Methylation
  • Piperidines / chemical synthesis*
  • Piperidines / metabolism*
  • Piperidines / pharmacokinetics
  • Radioligand Assay
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / metabolism*
  • Serotonin Antagonists / pharmacokinetics
  • Tomography, Emission-Computed

Substances

  • Carbon Radioisotopes
  • Fluorobenzenes
  • Hydrocarbons, Iodinated
  • Piperidines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • methyl iodide
  • volinanserin