Radioligands for the study of brain 5-HT1A receptors in vivo - Developmentof some new analogues of WAY

[Carbonyl-C-11]WAY-100635 (WAY) has proved to be a very useful radioligand for the imaging of brain 5-HT1A receptors in human brain in vivo with posit ron 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 a nd more sustained delivery to brain, is desirable since these properties mi ght lead to better biomathematical modelling of acquired PET data. There ar e also needs for other types of 5-HT1A receptor radioligands, for example, ligands sensitive to elevated serotonin levels, ligands labelled with longe r-lived fluorine-18 for distribution to "satellite" PET centres, and ligand s labelled with iodine-123 for single photon emission computerised tomograp hy (SPECT) imaging. Here we describe our progress toward these aims through the exploration of WAY analogues, including the development of [carbonyl-C -11]desmethyl-WAY (DWAY) as a promising, more brain-penetrant radioligand f or PET imaging of human 5-HT1A receptors, and (pyridinyl-6-halo)-analogues as promising leads for the development of radiohalogenated ligands. NUCL ME D BIOL 27;5:449-455, 2000. (C) 2000 Elsevier Science Inc. All rights reserv ed.