Development of a PET radioligand for the central 5-HT1B receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

Nucl Med Biol. 2011 Feb;38(2):261-72. doi: 10.1016/j.nucmedbio.2010.08.006. Epub 2010 Dec 3.


Introduction: The serotonin 1B (5-HT(1B)) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT(1B) receptor in the primate brain in vivo.

Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [(11)C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography.

Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/μmol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [(11)C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT(1B) receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics.

Conclusion: Candidate [(11)C]6, i.e., [(11)C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT(1B) receptors and was nominated for further preclinical characterization and PET examination in human subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / metabolism*
  • Animals
  • Biological Transport
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Carbon Radioisotopes
  • Humans
  • Isotope Labeling
  • Ligands
  • Macaca fascicularis
  • Positron-Emission Tomography / methods*
  • Radiochemistry / methods*
  • Receptor, Serotonin, 5-HT1B / metabolism*
  • Substrate Specificity


  • Amides
  • Carbon Radioisotopes
  • Ligands
  • Receptor, Serotonin, 5-HT1B