Radioligands for the study of brain 5-HT1A receptors in vivo -: Development of 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 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-HT1A 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-C-11]desmethyl-WAY (DWAY) as a promising, more brain-penetrant radioligand for PET imaging of human 5-HT1A receptors, and (pyridinyl-6-halo)-analogues as promising leads for the development of radiohalogenated ligands. NUCL MED BIOL 27;5:449-455, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.