二氧化矽空心球在核磁共振顯影上之應用

Abstract

近年來核磁共振造影(Magnetic Resonance Imaging, MRI)在醫療診斷上扮演極為重要的角色，核磁共振顯影劑的開發更是此領域相當重要的一環，核磁共振顯影劑的優劣影響診斷甚鉅，衡量顯影劑的好壞是根據弛緩率值(Relaxivity)與其生物毒性高低決定。本論文的貢獻在於提供低生物毒性之釓磷錯合物二氧化矽空球(GdPO4@SiO2)與釓金屬氧化物二氧化矽空心球(Gd2O3@HSN)，合成更佳的核磁共振顯影劑，有助於未來提升醫療診斷品質。 本研究中，以二氧化矽空心球包覆不同釓金屬化合物作為主軸，並依其合成方式分為兩個部分。第一部分我們利用改良後StÖber方式將釓金屬順磁性物質包入二氧化矽空心球中，並藉由調控磷酸二氫銨的濃度形成不同莫耳比的釓磷錯合物包入二氧化矽空球(GdPO4@SiO2)中，探討不同莫耳比釓磷錯合物奈米複合材料對於弛緩率的影響。透過穿透式電子顯微鏡、動力光散射儀、感應耦合電漿質譜儀及X光粉末繞射儀鑑定其組成結構。由於釓金屬(Gd3+)對人體具有相當毒性，而此釓磷錯合物的低溶解性，使得該複合材料降低其生物毒性，對於核磁共振顯影劑在人體應用極具潛力。 第二部分先以熱分解方法合成釓金屬氧化物再以配位體交換的方式將oleate的保護基置換成水溶性PVP保護基，接著再以微乳液合成法將此水溶性釓金屬氧化物包入二氧化矽空心球中，探討二氧化矽空心球中不同濃度的釓金屬氧化物對於弛緩率的影響。

In recent years, magnetic resonance imaging (MRI) is one of the paramount techniques in diagnostic and biomedical research, providing a nondestructive tool in examining soft tissues. Because of the relatively low sensitivity, contrast agents are often used in MRI diagnoses. Contrast agents can be divided into two groups: positive contrast agents and negative contrast agents. Positive contrast agents are mostly paramagnetic transition metals like Gd3+ ion, however, the free Gd3+ ion has been shown to be toxic both in vitro and in vivo studies. Therefore, chelation of Gd3+ ion is a way to avoid the toxicity for in vivo use. In first section, we synthesized GdPO4@SiO2-PEG500 nanoparticles based on the modified StÖber method.. By varying the concentration of NH4H2PO4, we obtained the GdPO4@SiO2 nanoparticles and investigate the effect on the relaxivities. The second section, we developed a water-in-oil (W/O) approach to incorporate PVP-stabilized gadolinium oxide nanoparticles in hollow silica nanospheres. Gadolinium oxide particles were synthesized by thermal decomposition method and then ligand exchange with PVP. By varying the concentration of PVP-stabilized Gd2O3 nanoparticles encapsulated in hollow silica nanosphere, we also investigated the effect on the relaxivities. These nanoparticles were characterized by TEM, relaxation measurements, DLS, XRD, FTIR and ICP-MS.