高灵敏19F磁共振和CT双模态成像探针的构筑及肿瘤影像分析

19F Magnetic resonance imaging (19F MRI) and X-ray computed tomography (CT) dual-modality imaging technique well remains the advantages of conventional 1H MRI/CT such as deep tissue penetration, high image contrast of soft tissue and good spatial resolution; meanwhile, it displays superiors merits such as high specificity, low background noise, possessing great potentials in precision diagnosis of deep pathological tissue. Generally, the signal intensity of 19F MRI is proportionally to the numbers of fluorine atoms as well as their mobility. Yet, normally increase of fluorine atoms often lead to decrease mobility of them and also the impairment of 19F MRI intensity. With respect to this issue, in this proposal, novel 19F-containing functional molecules would be prepared, which were further delicately equipped with inorganic nanocrystals that could be used as CT agents. Through manipulation of chain length, variation of functional group as well optimization of spatial layout of surface ligands, the mobility of ligands would be improved, so is the fluorine atom. Accordingly excellent relaxation performance of fluorine atom would be maintained while increasing the number of them. By further encapsulation with functionalized amphiphilic polymer, highly sensitive 19F MRI/CT dual-modality nanoprobes will be constructed and their application in deep-tissue tumor imaging would be explored. In view of the variety of inorganic nanoparticles, it anticipated that a universal design protocol for fabrication of different multimodal imaging probes would be developed, which would serve as new multimodal imaging techniques for early diagnosis of cancers.

19FMRI/CT双模态影像在保留传统1HMRI/CT技术组织穿透性深，软组织成像对比度高和空间分辨率高的优势的同时又具有特异性高、背景噪音低的特点，在深层病变组织精准诊疗方面具有重要意义。通常19FMRI信号强度与19F原子数目及其活动性呈正相关，而采用传统单一增加19F原子数的方法，常引起其活动性下降，导致信号减弱。针对这一关键问题，本课题拟设计合成新型的19F功能信号分子，并将其与无机纳米颗粒(具有CT成像功能)巧妙嫁接，从调控配体链长、改变官能团种类、优化表面配体空间几何布局入手，有效改善配体活动性，实现增加19F原子数目的同时保持其良好弛豫性能，并借助功能化双亲性高分子的包覆，构建出高灵敏19FMRI/CT双模态影像纳米探针。鉴于无机功能材料的多样性，本项目的实施可发展一种普适的方法用于构建不同模态影像探针，为癌症的早期超灵敏诊断提供多模态影像新技术。

分子影像技术为重大疾病早期诊断、实时评价治疗效果及实时原位示踪等方面发挥着重要的作用。发展多模态成像探针可克服不同成像模式局限性，实现优势互补，从而提高疾病诊断的准确度。在本项目的资助下，围绕活体影像分析，发展了系列具有多功能的探针：1)设计了具有跨尺度成像的多模探针(荧光/磁共振成像，1H/19F磁共振成像，CT/磁共振成像以及结合光声成像的多模成像探针；2) 设计具有病变部位微环境响应型多模成像探针，提高探针的特异性；3) 构建多模成像介导的纳米诊疗体系。共发表论文SCI论文15篇，包括Chem1篇，Adv.Funct.Mater.2篇，Anal.Chem.7篇。指导在研硕士5名，毕业硕士8名(1名获国家奖学金)，指导6名本科生毕业课题(1名获校级优秀毕业课题)，指导本科学生参加北京市第13届大学生化学实验竞赛，并荣获北京市一等奖。申请发明专利3项，授权1项，参与编写专著1项(8万字)，组织参与国内专题学术研讨会4次，做口头报告2次。