文章基本信息

标题：Preliminary Characterization and In Vivo Studies of Structurally Identical ¹⁸F- and ¹²⁵I-Labeled Benzyloxybenzenes for PET/SPECT Imaging of β-Amyloid Plaques
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作者：Yanping Yang ; Xiaoyang Zhang ; Mengchao Cui 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep12084
出版社：Springer Nature
摘要：With the assistance of molecular docking and 3D-QSAR models established previously, structurally identical ¹⁸F- and ¹²⁵I-labeled benzyloxybenzene derivatives were designed to achieve the early detection of A β plaques by PET/SPECT imaging. In competition binding assay, ligands 7a and 12a displayed high binding affinities to A β ₄₂ aggregates with K _i values of 19.5 nM and 23.9 nM, respectively. Specific plaque labeling was observed on the in vitro autoradiography of brain sections from AD patients and Tg mice. In biodistribution, [¹²⁵I]7a, [¹⁸F]7a, [¹²⁵I]12a and [¹⁸F]12a all exhibited high initial brain uptakes (>5% ID/g at 2 min). [¹²⁵I]7a and [¹²⁵I]12a cleared fast from the normal brain regions, while corresponding [¹⁸F]7a and [¹⁸F]12a showed slow washout rates. Dynamic microPET/CT and microSPECT/CT imaging data in normal ICR mice were in accordance with in vivo biodistribution results. In vivo metabolism results indicated that the different clearance profiles between the structurally identical ¹⁸F- and ¹²⁵I-labeled tracers could be attributed to different biochemical characteristics of the radiometabolites. Radioiodinated benzyloxybenzene derivatives exhibited good in vivo biostability in brain. Ex vivo autoradiography further confirmed the strong in vivo A β labeling ability of [¹²⁵I]7a. These new fluorinated and iodinated benzyloxybenzenes can develop into PET/SPECT dual imaging agents targeting A β plaques.