Fused Cycloheptatriene–BODIPY Is a High-Performance Near-Infrared Probe to Image Tau Tangles

• Published in: Journal of medicinal chemistry 2022-11, Vol.65 (21), p.14527-14538
• Main Authors: Xie, Tianxin, Li, Yuying, Tian, Chuan, Yuan, Chang, Dai, Bin, Wang, Shubo, Zhou, Kaixiang, Liu, Jiaqi, Tan, Hongwei, Liang, Yi, Dai, Jiapei, Chen, Baian, Cui, Mengchao
• Format: Article
• Language: English
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.2c00859

Neurofibrillary tangles (NFTs), which are composed of abnormally hyperphosphorylated Tau, are one of the main pathologic hallmarks of Alzheimer’s disease and other tauopathies. The fluorescent imaging probes currently used to target NFTs cannot distinguish them well from β-amyloid plaques, thus limiting their utility to diagnose diseases. Here, we developed a fused cycloheptatriene–BODIPY derivative (TNIR7-1A) that displays properties favorable for near-infrared (NIR) imaging with high affinity and specificity to NFTs in vitro. In addition, TNIR7-1A effectively penetrated the blood–brain barrier and clearly distinguished tauopathy in transgenic mice (rTg4510) from control mice using NIR fluorescence imaging in vivo. The sensitivity and specificity of TNIR7-1A for NFTs were confirmed ex vivo by fluorescence staining of the tauopathy mouse model, while molecular docking studies indicated that TNIR7-1A bound to NFTs through hydrophobic interactions. These results suggest that TNIR7-1A can act as a high-performance probe to detect NFTs in vitro and in vivo selectively.