標題: 釓雙胺共軛幾丁聚醣之雙性高分子核磁共振顯影劑:分子結構分析與動物顯影
A New Type of Gadodiamide-Conjugated Chitosan Amphiphiles For MR Imaging: Molecular Structural Analysis and Animal Imaging
作者: 戈一平
劉典謨
Ko, Yi-Ping
Liu, Dean-Mo
材料科學與工程學系所
關鍵字: 顯影劑;高分子;磁振造影;幾丁聚醣;contrast agent;macromolecule;MRI;chitosan
公開日期: 2017
摘要: 癌症乃近幾十年來主要死因,一部份原因為早期診斷的困難。在臨床實踐上,不具 游離輻射的核磁共振造影,是一個強力的非侵入性癌症診斷工具,核磁共振造影常常會使用顯影劑來使人體的影像清晰,而近來最常使用的一類顯影劑為含釓顯影劑,是一種其配位中心為釓(III)離子的錯合物,需要注意的是,游離的釓(III)離子對人體是有毒性的,許多數據顯示出若在腎功能不全的病人身上使用含釓顯影劑,則可能導致嚴重的副作用-腎因性全身纖維化。
為了提高顯影劑的安全性,我們透過縮合反應,將本實驗室開發的具高度生物相容性高分子與臨床上常用的含釓顯影劑釓雙胺結合在一起,成為新穎高分子顯影劑,兩個 最重要的優勢為比釓雙胺具有更高的顯影能力以及低劑量即能使用,透過核磁共振造影的結果發現,將新穎高分子顯影劑經由尾靜脈注射進小鼠體內,其腎臟的對比增強明顯高於釓雙胺,此外,新穎高分子顯影劑可以增強異位移植腫瘤的對比度,產生標靶導向的作用,而能在早期階段發現腫瘤。
Cancer has been the leading cause of death over decades worldwide, one of the main reasons is its difficulty of tumor detection in early stage, and has long been a prime research objective in the field from materials science to nanomedicine. In clinical practices, magnetic resonance imaging (MRI), which uses non-ionizing radiation, is a non-invasive and powerful diagnostic tool for cancer detection. MRI often uses contrast agent to make the images of human body clear. The current commonly used contrast agent is gadolinium(64Gd)-based contrast agent (GBCA), which is a coordination complex and its coordination center is Gd3+. It is important to note that de-chelated Gd3+ ions are toxic to the human body. More data show that if GBCA is used in patients with poor renal function, it will lead to an adverse effect, nephrogenic systemic fibrosis.
To improve the biosafety of GBCA, we have combined amphiphilic chitosan, which is a highly biocompatible polymer developed in our lab, and gadodiamide, the contrast agent frequently used in clinics, through condensation reaction and become novel macromolecular MRI contrast agent. The most important advantages for this newly-synthesized macromolecular MRI contrast agent are higher contrast enhancement and lower dose than the native Gadodiamide used. Through the results of MRI, injection of the macromolecular MRI contrast agent in the tail vein of mice clearly demonstrated that the contrast enhancement of the kidney was much higher than that of gadodiamide. Additionally, the experimental results showed excellent active targeting contrast image toward xenograft tumor in-vivo, suggesting a potential development in clinical translation for tumor diagnosis.
URI: http://etd.lib.nctu.edu.tw/cdrfb3/record/nctu/#GT070451512
http://hdl.handle.net/11536/141674
Appears in Collections:Thesis