机构：[1]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China.[2]Department of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.北京大学深圳医院深圳市康宁医院深圳市南山区人民医院深圳医学信息中心中国医学科学院肿瘤医院深圳医院[3]School of Pharmaceutical Science, Capital Medical University, Beijing 100069, China.[4]Institute of Biomedical Engineering, Shenzhen Graduate School, Peking University, Shenzhen 518055, China.[5]Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.首都医科大学宣武医院
Accurate quantification of amyloid beta (Aβ) plaques is an important indicator for Alzheimer's disease diagnosis and treatment. For this purpose, new highly sensitive Aβ tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]BIBD-124 and [18F]BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]BIBD-124/127 were similar to that of [18F]AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]BIBD-124 could monitor Aβ plaques similar to [18F]AV45. Besides, the imaging contrast of [18F]BIBD-124 is better than that of [18F]AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]BIBD-124 is expected to be a promising radiotracer of Aβ plaques for further clinical trials.
基金：
Beijing Natural Science
Foundation (7222299) and the National Natural Science
Foundation of China (81701753 and 82102115). The PET
imaging part of this research was also supported by the project
“the third foster plan in 2019” Molecular Imaging Probe
Preparation and Characterization of Key Technologies and
Equipment (ZDKJ20190305003).
第一作者机构：[1]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zheng Wei,Huang Yong,Chen Hualong,et al.Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aβ Plaques[J].ACS CHEMICAL NEUROSCIENCE.2023,14(5):988-1003.doi:10.1021/acschemneuro.3c00025.
APA：
Zheng Wei,Huang Yong,Chen Hualong,Jiang Zeng,Yu Ziyue...&Wu Zehui.(2023).Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aβ Plaques.ACS CHEMICAL NEUROSCIENCE,14,(5)
MLA：
Zheng Wei,et al."Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aβ Plaques".ACS CHEMICAL NEUROSCIENCE 14..5(2023):988-1003
