超顺磁性氧化铁纳米颗粒作为肝癌早期诊断MRI对比剂的放大合成研究

发布时间：2018-11-12 14:46

【摘要】：由于中晚期的癌症治疗难度很大,而且复发率极高。因此癌症的治疗需要尽量做到早发现早诊断早治疗。而早期肿瘤的检测要求医疗检测手段具有无创、需对病人身体各脏器各角度各平面成像,且要求有高清晰度的成像效果以实现对病灶部位进行准确的定位等特点,磁共振(MRI)成像技术能很好满足这些临床检查要求。因此这些特点使得MRI成像技术在肿瘤的早期诊断具有很大的价值。超顺磁性氧化铁颗粒(SPIO)作为最具潜力的钆(Gd)的顺磁性对比剂替代品,一直是MRI对比剂的热门选择。而由于原本上市的SPIO类型的T2对比剂AMI-25及SHU-555A相继退出中国市场,因此国内目前SPIO类型的T2类核磁对比剂几乎处于空白状态,研究SPIO类型的MRI对比剂在临床上具有广阔的应用前景。本文的目的是建立一种具有临床MRI成像应用潜力的水溶性SPIO纳米颗粒,并通过放大合成规模,为其临床应用提供理论和技术支持。本文主要研究结果有:1)通过小剂量的油相和水相合成方法,获得了水溶性的SPIO纳米颗粒,具有超顺磁性且分散性良好。2)将这一合成反应方法进一步放大合成规模,通过对放大过程的研究及放大过程中的参数控制,实现了放大规模的最佳合成工艺确定,为提高SPIO纳米颗粒的临床应用性提供了基础。3)将放大合成所得的产物用于小鼠肝硬化和裸鼠皮下瘤模型的MRI成像造影,成像结果显示合成出的水溶性SPIO纳米颗粒具有显著提高成像分辨率的功能,为癌症早期的细微病变检出提供了可能性。
[Abstract]:Because of advanced cancer treatment is very difficult, and the recurrence rate is extremely high. Therefore, the treatment of cancer needs to be early detection, early diagnosis and early treatment. The detection of early tumor requires noninvasive medical examination, imaging of every angle and plane of each organ of the patient, and high definition imaging effect in order to realize the accurate location of the lesion, and so on. Magnetic resonance (MRI) imaging can well meet these clinical requirements. Therefore, MRI imaging has great value in the early diagnosis of tumor. Superparamagnetic iron oxide (SPIO) particles, as the most promising paramagnetic contrast agent for gadolinium (Gd), have always been the hot choice of MRI contrast agents. However, AMI-25 and SHU-555A, the T2 contrast agents of SPIO type, which were originally listed on the market, have been withdrawn from the Chinese market one after another, so at present, the T2 type nuclear magnetic contrast agents of SPIO type in China are almost blank. The study of SPIO type MRI contrast agent has a broad prospect in clinical application. The aim of this paper is to establish a kind of water-soluble SPIO nanoparticles with the potential of clinical MRI imaging and to provide theoretical and technical support for its clinical application by enlarging the scale of synthesis. The main results are as follows: 1) Water-Soluble SPIO nanoparticles were obtained by low dose oil phase and water phase synthesis methods, with superparamagnetic and good dispersibility. 2) the synthesis method was further scaled up. Through the study of the amplification process and the parameter control in the amplification process, the optimal synthesis process of the large scale is determined. It provides a basis for improving the clinical application of SPIO nanoparticles. 3) the amplified products are used in MRI imaging of liver cirrhosis and subcutaneous tumor models in nude mice. The imaging results show that the synthesized water-soluble SPIO nanoparticles can significantly improve the imaging resolution and provide the possibility for the detection of small lesions in the early stage of cancer.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.7;TB383.1

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