Hydroxyethyl-Modified Cycloheptatriene-BODIPY Derivatives as Specific Tau Imaging Probes

Near-infrared fluorescence (NIRF) imaging as an exquisite sensitive, high spatial-resolution, and real-time tool plays an important role in visualizing pathologies in the brain. In this study, we designed and synthesized a series of NIR probes of hydroxyethyl cycloheptatriene-BODIPY derivatives that have demonstrated strong binding specificity to native neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brain sections. The improved hydrophilicity of TNIR7-9 and TNIR7-11 resulted in faster clearance rates from healthy brains (4.2 and 10.9, respectively) compared to previously reported compounds. Furthermore, TNIR7-13, which features a fluorinated modification, exhibited a high binding affinity to Tau aggregates (K_d = 11.8 nM) and held promise for future PET studies.