Pike V W, Halldin C, Wikström H, Marchais S, McCarron J A, Sandell J, Nowicki B, Swahn C G, Osman S, Hume S P, Constantinou M, Andrée B, Farde L
MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, London W12 ONN, United Kingdom.
Nucl Med Biol. 2000 Jul;27(5):449-55. doi: 10.1016/s0969-8051(00)00110-4.
[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.
[羰基-(11)C]WAY-100635（WAY）已被证明是一种非常有用的放射性配体，可通过正电子发射断层扫描（PET）在人体内对脑5-HT(1A)受体进行活体成像。WAY目前正广泛应用于临床研究和药物开发。然而，WAY会迅速从血浆中清除，并且代谢也很快。由于这些特性可能会导致对获取的PET数据进行更好的生物数学建模，因此需要一种具有更高且更持续的脑内递送的类似放射性配体。还需要其他类型的5-HT(1A)受体放射性配体，例如，对血清素水平升高敏感的配体、用半衰期更长的氟-18标记以便分发给“卫星”PET中心的配体，以及用碘-123标记用于单光子发射计算机断层扫描（SPECT）成像的配体。在此，我们通过探索WAY类似物来描述我们在实现这些目标方面的进展，包括开发[羰基-(11)C]去甲基-WAY（DWAY）作为一种有前景的、脑渗透性更强的用于人类5-HT(1A)受体PET成像的放射性配体，以及（吡啶基-6-卤代）类似物作为放射性卤化配体开发的有前景的先导化合物。
