化学
正电子发射断层摄影术
标准摄取值
Pet成像
Tau病理学
体内
核医学
阿尔茨海默病
病理
医学
疾病
生物
生物技术
作者
Nan Wu,Longfei Zhang,Xiaojun Zhang,Qilei Zhang,Jiaqi Liu,Yuying Li,Xiao‐Xin Yan,Yi Liang,Jinming Zhang,Mengchao Cui
标识
DOI:10.1021/acs.molpharmaceut.3c00717
摘要
This study focused on designing and evaluating Tau-PET tracers for noninvasive positron emission computed tomography (PET) imaging of neurofibrillary tangles (NFTs), a hallmark pathology of Alzheimer’s disease (AD). The tracers were synthesized with a 2-styrylquinoxaline scaffold and varying lengths of FPEG chains. The compound [18F]15, which had two ethoxy units, showed high affinity for recombinant K18-Tau aggregates (Ki = 41.48 nM) and the highest selectivity versus Aβ1–42 aggregates (8.83-fold). In vitro autoradiography and fluorescent staining profiles further validated the binding of [18F]15 or 15 toward NFTs in brain sections from AD patients and Tau-transgenic mice. In normal ICR mice, [18F]15 exhibited an ideal initial brain uptake (11.21% ID/g at 2 min) and moderate washout ratio (2.29), and micro-PET studies in rats confirmed its ability to penetrate the blood–brain barrier with the peak SUV value of 1.94 in the cortex. These results suggest that [18F]15 has the potential to be developed into a useful Tau-PET tracer for early AD diagnosis and evaluation of anti-Tau therapeutics.
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