Amyloid-β oligomers (AβOs) enrichment in brain is highly related to Alzheimer’s pathogenesis, but tracing them in the brain by imaging technique is still a great challenge due to their heterogeneity and metastability. Herein, a new near-infrared (NIR) fluorescent probe, namely, PTO-41, was designed and synthesized to specifically target AβOs. PTO-41 possesses excellent functional properties including optimal fluorescent properties (emission maxima at 680 nm upon interacting with AβOs), high affinity (K_d = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain_{2 min}/brain_{60 min} = 5.0). Furthermore, PTO-41 exhibits a high sensitivity toward AβOs in vitro phantom imaging experiments. More importantly, PTO-41 shows great capacity to differentiate between 4-month-old APP/PS1 model mice from age-matched control mice using in vivo imaging. In summary, PTO-41 almost meets all the requirements as a versatile NIR fluorescent probe for the detection of AβOs both in vitro and in vivo.

大脑中淀粉样β-低聚物（AβOs）的富集与阿尔茨海默氏症的发病机理高度相关，但是由于其异质性和亚稳定性，通过成像技术在大脑中追踪它们仍然是一个巨大的挑战。在本文中，设计并合成了新的近红外（NIR）荧光探针PTO-41以特异性靶向AβOs。PTO-41具有出色的功能特性，包括最佳的荧光特性（与AβOs相互作用时在680 nm处发射最大值），高亲和力（K _d  = 349 nM），低细胞毒性，所需的亲脂性（log P = 2.24）和快速洗出来自大脑（大脑_2分钟/大脑_60分钟 = 5.0）。此外，PTO-41在体外幻影成像实验中对AβOs具有很高的敏感性。更重要的是，PTO-41使用体内成像技术，具有区分4个月大的APP / PS1模型小鼠和年龄匹配的对照小鼠的巨大能力。总而言之，PTO-41几乎可以满足作为通用NIR荧光探针在体外和体内检测AβOs的所有要求。