期刊
MOLECULES
卷 28, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/molecules28155769
关键词
[I-125]INFT; [I-125]IPPI; post-mortem human Tau; Alzheimer's disease; neurofibrillary tangles; autoradiography
This study aimed to develop and evaluate a novel radioiodinated tracer, [I-125]INFT, for binding to Tau protein in postmortem human AD brain. The results showed that [I-125]INFT binding correlated with the presence of Tau and could be used as an imaging agent for AD.
Aggregation of Tau protein into paired helical filaments causing neurofibrillary tangles (NFT) is a neuropathological feature in Alzheimer's disease (AD). This study aimed to develop and evaluate the effectiveness of a novel radioiodinated tracer, 4-[I-125]iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)pyridine ([I-125]INFT), for binding to Tau protein in postmortem human AD brain. Radiosynthesis of [I-125]INFT was carried out using electrophilic destannylation by iodine-125 and purified chromatographically. Computational modeling of INFT binding on Tau fibril was compared with IPPI. In vitro, autoradiography studies were conducted with [I-125]INFT for Tau in AD and cognitively normal (CN) brains. [I-125]INFT was produced in >95% purity. Molecular modeling of INFT revealed comparable binding energies to IPPI at site-1 of the Tau fibril with an affinity of IC50 = 7.3 x 10(-8) M. Binding of [I-125]INFT correlated with the presence of Tau in the AD brain, confirmed by anti-Tau immunohistochemistry. The ratio of average grey matter (GM) [I-125]INFT in AD versus CN was found to be 5.9, and AD GM/white matter (WM) = 2.5. Specifically bound [I-125]INFT to Tau in AD brains was displaced by IPPI (>90%). Monoamine oxidase inhibitor deprenyl had no effect and clorgyline had little effect on [I-125]INFT binding. [I-125]INFT is a less lipophilic imaging agent for Tau in AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据