Zhuang Zhi-Ping, Kung Mei-Ping, Wilson Alan, Lee Chi-Wan, Plössl Karl, Hou Catherine, Holtzman David M, Kung Hank F
Department of Radiology, University of Pennsylvania, 3700 Market Street, Room 305, Philadelphia, Pennsylvania 19104, USA.
J Med Chem. 2003 Jan 16;46(2):237-43. doi: 10.1021/jm020351j.
A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related derivatives were prepared. An in vitro binding study with preformed A beta aggregates showed that 16(IMPY) and its bromo derivative competed with binding of 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for A beta aggregates, with high binding affinities (K(i) = 15 and 10 nM, respectively). In vitro autoradiography of brain sections of a transgenic mouse (Tg2576) with [125I]16(IMPY) displayed high selective binding to amyloid-like structures, comparable to that observed by staining with thioflavin-S visualized under fluorescence. In vivo biodistribution after an intravenous injection of [125I]16(IMPY) in normal mice showed a high initial brain uptake and fast washout, indicating a low background activity associated with this iodinated ligand. Taken together, the data suggests that [123I]16(IMPY) may be useful for imaging A beta aggregates in patients with Alzheimer's disease.
制备了一系列新型的β-淀粉样蛋白（Aβ）聚集体特异性配体，即2-(4'-二甲基氨基苯基)-6-碘咪唑并[1,2-a]吡啶（16(IMPY)）及其相关衍生物。一项针对预先形成的Aβ聚集体的体外结合研究表明，16(IMPY)及其溴代衍生物能与已知的Aβ聚集体配体2-(4'-二甲基氨基苯基)-6-碘苯并噻唑（[125I]7(TZDM)）竞争结合，且具有高结合亲和力（K(i)分别为15和10 nM）。用[125I]16(IMPY)对转基因小鼠（Tg2576）脑切片进行体外放射自显影显示，其与淀粉样结构具有高度选择性结合，与硫黄素-S染色后在荧光下观察到的情况相当。在正常小鼠静脉注射[125I]16(IMPY)后的体内生物分布显示，其最初脑摄取高且清除快，表明该碘化配体的背景活性低。综合来看，数据表明[123I]16(IMPY)可能有助于对阿尔茨海默病患者的Aβ聚集体进行成像。
