In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET radioligand in nonhuman primate

Bioorg Med Chem Lett. 2017 Jan 1;27(1):21-23. doi: 10.1016/j.bmcl.2016.11.043. Epub 2016 Nov 16.

Abstract

We recently reported the radiosynthesis and in vitro evaluation of [18F]-2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-(2-fluoroethoxy)benzyl)ethanamine, ([18F]FECIMBI-36) or ([18F]1), an agonist radioligand for 5HT2A/2C receptors in postmortem samples of human brain. Herein we describe the in vivo evaluation of [18F]FECIMBI-36 in vervet/African green monkeys by PET imaging. PET images show that [18F]FECIMBI-36 penetrates the blood-brain barrier and a low retention of radioactivity is observed in monkey brain. Although the time activity curves indicate a somehow heterogeneous distribution of the radioligand in the brain, the low level of [18F]FECIMBI-36 in brain may limit the use of this tracer for quantification of 5-HT2A/2C receptors by PET.

Keywords: 5-HT; 5-HT(2A/2C)R; Agonist; PET; Radiotracer.

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Ethylamines / chemical synthesis
  • Ethylamines / chemistry
  • Ethylamines / pharmacology*
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacology*
  • Humans
  • Ligands
  • Magnetic Resonance Imaging
  • Male
  • Molecular Structure
  • Positron-Emission Tomography*
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin 5-HT2 Receptor Agonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Agonists / chemistry
  • Serotonin 5-HT2 Receptor Agonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • ((18)F)-2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-(2-fluoroethoxy)benzyl)ethanamine
  • Ethylamines
  • Fluorine Radioisotopes
  • Ligands
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists