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

Yuying Li; Chuan Tian; Tianxin Xie; Qi-Lei Zhang; Jiaqi Liu; Xiao-Xin Yan; Jiapei Dai; Yi Liang; Mengchao Cui

doi:10.1021/acsmedchemlett.3c00248

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

ACS Med Chem Lett. 2023 Jul 11;14(8):1108-1112. doi: 10.1021/acsmedchemlett.3c00248. eCollection 2023 Aug 10.

Authors

Yuying Li¹, Chuan Tian¹, Tianxin Xie¹, Qi-Lei Zhang², Jiaqi Liu³, Xiao-Xin Yan², Jiapei Dai⁴, Yi Liang³, Mengchao Cui^{1

5}

Affiliations

¹ Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing 100875, China.
² Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha 410013, China.
³ College of Life Sciences, Taikang Center for Life and Medical Science, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, China.
⁴ Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, China.
⁵ Center for Advanced Materials Research, Beijing Normal University, Zhuhai 519087, China.

PMID: 37583810
PMCID: PMC10424304 (available on 2024-08-10)
DOI: 10.1021/acsmedchemlett.3c00248

Abstract

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.