机构：[1]Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing 100875, China[2]Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院[3]Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China[4]Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, China
An oligoethyleneoxy linker was introduced for conjugation between Tc-99m/Re-bis(aminoethanethiol) (BAT) and beta-amyloid (A beta) binding scaffolds. Rhenium complexes exhibited high to moderate binding affinity to A beta(1-42) aggregates and efficient fluorescent staining to A beta plaques in brain tissue. After radiolabeling, the Tc-99m-labeled probes revealed improved brain pharmacokinetics in normal ICR mice. Probe [Tc-99m]15 with potent binding affinity (K-i = 13.4 nM) and the highest initial brain uptake (2.10% ID/g at 2 min) in normal ICR mice was evaluated further. In vitro autoradiography showed specific labeling of A beta plaques by [Tc-99m]15 in transgenic (Tg) mouse brain tissue. Ex vivo autoradiography further demonstrated its efficient labeling of A beta plaques in a living Tg mouse. In vivo single photon emission computed tomography (SPECT)/CT imaging in six rhesus monkeys revealed remarkably improved brain uptakes (1.94-2.63% ID within 20 min) of [Tc-99m]15, making it highly potential to be used in humans for A beta plaques imaging in the brain.
基金：
the National Natural Science Foundation of China (Nos. 21571022 and 81571230)
the National Science and Technology Major Projects for Major New Drugs Innovat ion and Development (No. 2014ZX09507007-002).
Beijing Municipal Administration of Hospitals Incubating Program (No. PX2016016).
第一作者机构：[1]Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing 100875, China
通讯作者：
通讯机构：[1]Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing 100875, China[2]Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China[3]Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China
推荐引用方式(GB/T 7714)：
Xiaoyang Zhang ,Yaqin Hou ,Cheng Peng ,et al.Oligoethyleneoxy-Modified Tc-99m-Labeled beta-Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography[J].JOURNAL OF MEDICINAL CHEMISTRY.2018,61(3):1330-1339.doi:10.1021/acs.jmedchem.7b01834.
APA：
Xiaoyang Zhang,,Yaqin Hou,,Cheng Peng,,Chu Wang,,Xiang Wang,...&Mengchao Cui,.(2018).Oligoethyleneoxy-Modified Tc-99m-Labeled beta-Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography.JOURNAL OF MEDICINAL CHEMISTRY,61,(3)
MLA：
Xiaoyang Zhang,,et al."Oligoethyleneoxy-Modified Tc-99m-Labeled beta-Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography".JOURNAL OF MEDICINAL CHEMISTRY 61..3(2018):1330-1339
医学