基于NaGdF4纳米晶体的磁共振分子影像探针的构建与性质研究

项目名称： 基于NaGdF4纳米晶体的磁共振分子影像探针的构建与性质研究

项目编号： No.21203211

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 物理化学

项目作者： 侯毅

作者单位： 中国科学院化学研究所

项目金额： 27万元

中文摘要： 磁共振成像技术是目前生物医学检测及肿瘤临床诊断的主要手段之一，为提高成像对比度，磁共振成像造影剂被广泛使用。然而，Gd-DTPA等顺磁离子络合物小分子造影剂存在血液代谢时间短，释放顺磁离子毒副作用高等缺点。因此，发展新型高灵敏度磁共振造影剂，进而构建分子影像探针已经成为全世界科学家所关注的热点。本项目拟以顺磁性NaGdF4纳米晶体作为T1加权磁共振分子影像探针的应用为背景，探索尺寸可控的单分散性NaGdF4纳米晶体和功能化的PEG配体的制备方法，并通过表面配体交换获得具有高水相分散性、胶体稳定性的顺磁性PEG-NaGdF4纳米晶体，然后通过与抗体耦联，获得具有抗体靶向的分子影像探针。进一步结合动物成像实验，系统研究NaGdF4纳米晶体尺寸和表面配体化学结构对纳米材料磁学性质、生物体内分布与代谢过程及与肿瘤靶向识别的影响，以期构建抗体靶向的NaGdF4纳米晶体磁共振影像探针。

中文关键词： NaGdF4 纳米晶体；聚乙二醇配体；配体置换；磁共振成像；分子影像探针

英文摘要： Magnetic resonance imaging (MRI) is a robust analytical technology in many areas of biomedical research, and diagnosis of diseases such as cancer. To meet the sensitivity requirement of the technique, contrast agents are always used in MRI assays. Gd-DTPA is a widely used MRI contrast agent in current clinical diagnosis. However, there are some drawbacks such as too short metabolism cycle and obvious side effects, which will limit the application of this small molecular contrast agent. To overcome these drawbacks, developing new contrast agents with appropriate retention time in body, low toxicity and tumor targeting, has received increasing attention. This proposal describes research on the synthesis, characterization and biofunctionalization of a new contrast agent to be employed in MRI of tumor. We propose to synthesize narrow distribution sodium gadolinium tetrafluoride (NaGdF4) nanocrystals with different diameters and functionalized PEG ligands, and to transform the hydrophobic NaGdF4 nanocrystals into the hydrophilic via ligand exchange. For targeted attaching with tumor, we also propose to develop the synthetic methodology to attach the nanocrystals to monoclonal antibody. The contrast effect of the NaGdF4 nanocrystal will be evaluated by in vitro and in vivo MRI detections. The effect of nanocrystal siz

英文关键词： NaGdF4 nanocrystal；poly(ethylene glycol) ligand；ligand exchange；magnetic resonance imaging；molecular imaging probes