Radioligands for the study of brain 5-HT(1A) receptors in vivo--development of some new analogues of way

Nucl Med Biol. 2000 Jul;27(5):449-55. doi: 10.1016/s0969-8051(00)00110-4.

Abstract

[Carbonyl-(11)C]WAY-100635 (WAY) has proved to be a very useful radioligand for the imaging of brain 5-HT(1A) receptors in human brain in vivo with positron emission tomography (PET). WAY is now being applied widely for clinical research and drug development. However, WAY is rapidly cleared from plasma and is also rapidly metabolised. A comparable radioligand, with a higher and more sustained delivery to brain, is desirable since these properties might lead to better biomathematical modelling of acquired PET data. There are also needs for other types of 5-HT(1A) receptor radioligands, for example, ligands sensitive to elevated serotonin levels, ligands labelled with longer-lived fluorine-18 for distribution to "satellite" PET centres, and ligands labelled with iodine-123 for single photon emission computerised tomography (SPECT) imaging. Here we describe our progress toward these aims through the exploration of WAY analogues, including the development of [carbonyl-(11)C]desmethyl-WAY (DWAY) as a promising, more brain-penetrant radioligand for PET imaging of human 5-HT(1A) receptors, and (pyridinyl-6-halo)-analogues as promising leads for the development of radiohalogenated ligands.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Chemistry*
  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Humans
  • Ligands
  • Piperazines / metabolism*
  • Pyridines / metabolism*
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / metabolism*
  • Tomography, Emission-Computed

Substances

  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Ligands
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide