Synthesis and biological evaluation of novel technetium-99m-labeled phenylquinoxaline derivatives as single photon emission computed tomography imaging probes targeting β-amyloid plaques in Alzheimer's disease
作者:Shimpei Iikuni、Masahiro Ono、Keiichi Tanimura、Hiroyuki Watanabe、Masashi Yoshimura、Hideo Saji
DOI:10.1039/c6ra28395k
日期:——
The development of an imaging probe targeting β-amyloid (Aβ) plaques in Alzheimer's disease labeled with technetium-99m, the most commonly used radioisotope for clinical diagnoses, has been strongly anticipated. In this study, we synthesized three novel 99mTc complexes with the phenylquinoxaline scaffold and evaluated their properties for imaging Aβ plaques. The 99mTc and corresponding Re complexes
人们强烈期望开发出针对以in-99m标记的阿尔茨海默氏病中针对β淀粉样蛋白(Aβ)斑块的成像探针,这是临床诊断中最常用的放射性同位素。在这项研究中,我们合成了三种新颖的99m Tc配合物与苯基喹喔啉骨架,并评估了它们对Aβ斑块成像的特性。的99米Tc和对应Re配合物与双(氨基乙硫醇)(BAT)作为螯合配位体合成的。在体外使用重组Aβ(1-42)聚集体进行结合亲和力测定中,99m Tc标记的N,N-二甲基化苯基喹喔啉衍生物(99mTc-BAT-C3-PQ-1)和相应的Re复合物对Aβ(1-42)聚集体表现出足够的亲和力。对正常小鼠进行的体内生物分布研究表明,99m Tc-BAT-C3-PQ-1显示出适度的初始大脑摄取和合理的大脑清除能力。一种体外放射自显影检查有99米锝-BAT-C3-PQ-1显示Aβ斑块的脑组织切片的显着标签从的Tg2576转基因小鼠,但不是年龄匹配的对照。99m Tc-B