Department of Anatomical Pathology, The Alfred Hospital, Victoria 3181, Australia.
Inorg Chem. 2020 Aug 17;59(16):11658-11669. doi: 10.1021/acs.inorgchem.0c01520. Epub 2020 Jul 28.
Alzheimer's disease is characterized by the presence of extracellular amyloid-β plaques. Positron emission tomography (PET) imaging with tracers radiolabeled with positron-emitting radionuclides that bind to amyloid-β plaques can assist in the diagnosis of Alzheimer's disease. With the goal of designing new imaging agents radiolabeled with positron-emitting copper-64 radionuclides that bind to amyloid-β plaques, a family of bis(thiosemicarbazone) ligands with appended substituted stilbenyl functional groups has been prepared. The ligands form charge-neutral and stable complexes with copper(II). The new ligands can be radiolabeled with copper-64 at room temperature. Two lead complexes were demonstrated to bind to amyloid-β plaques present in post-mortem brain tissue from subjects with clinically diagnosed Alzheimer's disease and crossed the blood-brain barrier in mice. The work presented here provides strategies to prepare compounds with radionuclides of copper that can be used for targeted brain PET imaging.
阿尔茨海默病的特征是存在细胞外淀粉样β斑块。用放射性核素标记的正电子发射断层扫描 (PET) 示踪剂与淀粉样β斑块结合，可辅助诊断阿尔茨海默病。为了设计新的成像剂，用放射性核素铜-64 标记与淀粉样β斑块结合的正电子发射放射性核素，已经制备了一系列带有附加取代芪基官能团的双（硫代缩氨基脲）配体。配体与铜 (II) 形成电荷中性且稳定的配合物。新型配体可在室温下用铜-64 进行放射性标记。有两项研究表明，两种先导复合物可与临床诊断为阿尔茨海默病的受试者死后脑组织中的淀粉样β斑块结合，并在小鼠体内穿过血脑屏障。本文提供了用铜放射性核素制备可用于靶向脑 PET 成像的化合物的策略。
