F-18 stilbenes as PET imaging agents for detecting beta-amyloid plaques in the brain.
F-18 stilbenes as PET imaging agents for detecting beta-amyloid plaques in the brain.
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DOI：
10.1021/jm050166g
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发表时间：
2005-09
影响因子：
7.3
通讯作者：
Wei Zhang;S. Oya;M. Kung;C. Hou;D. Maier;H. Kung
中科院分区：
文献类型：
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作者：
Wei Zhang;S. Oya;M. Kung;C. Hou;D. Maier;H. Kung
靶向β-淀粉样蛋白（Abeta）的显像剂可能有助于诊断和治疗阿尔茨海默病（AD）患者。化合物 3e 和 4e 是氟化二苯乙烯衍生物，对 AD 脑匀浆中的 Abeta 斑块表现出高结合亲和力（Ki 分别 = 15 +/- 6 和 5.0 +/- 1.2 nM）。 [18F]3e 和 [18F]4e 在正常小鼠体内的生物分布表现出优异的脑渗透性（2 分钟时为 5.55% 和 9.75% 剂量/g），并且观察到快速的脑冲洗，特别是 [18F]4e（60 分钟时为 0.72% 剂量/g）。他们还在 APP/PS1 或 Tg2576 转基因小鼠（AD 动物模型）中显示了体内斑块标记。死后 AD 脑切片的放射自显影和 AD 匀浆结合研究证实了与 Abeta 斑块的选择性和特异性结合特性。总之，初步结果强烈表明这些氟化二苯乙烯衍生物[18F]3e和[18F]4e是研究AD患者的Abeta斑块成像剂的合适候选者。
Imaging agents targeting beta-amyloid (Abeta) may be useful for diagnosis and treatment of patients with Alzheimer's disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for Abeta plaques in AD brain homogenates (Ki = 15 +/- 6 and 5.0 +/- 1.2 nM, respectively). In vivo biodistributions of [18F]3e and [18F]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75% dose/g at 2 min), and rapid brain washouts were observed, especially for [18F]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to Abeta plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [18F]3e and [18F]4e, are suitable candidates as Abeta plaque imaging agents for studying patients with AD.