A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT1A receptor PET radioligands

An outline is given of the developments that led to the identification of [O-methyl-C-11]WAY-100635 (4) as the first useful PET ligand for imaging serotonin(1A) (5-HT1A) receptors in the living human brain. Recent attempts to develop 5-HT1A receptor radioligands superior to 4 are reviewed, and [carbonyl[C-11]WAY-100635 (6) has been shown to be the best currently available radioligand for human studies. Of other C-11-radiolabelled compounds, [O-methyl-C-11](R,S)-CPC-222 (9), DWAY (8), and [C-11]NAD-299 (14) all demonstrate specific binding to 5-HT1A receptors in animals and warrant further expedited studies in humans. The trans-fluorocyclohexane, 12, and fluorobenzene, [F-18]p-MPPF 13, are highlighted as examples of promising F-18-labelled ligands. NUCL MED BIOL 27;5:441-447, 2000, (C) 2000 Elsevier Science Inc. All rights reserved.