以19F MRI偵測過氧亞硝酸根陰離子之釓金屬錯合物磁振造影對比劑 [Gd(DO3A-CF3)]之合成研究

Abstract

過氧亞硝酸根陰離子和敗血性休克、癌症、以及神經退化性疾病、發炎反應等有高度的相關性，研究體內過氧亞硝酸根陰離子的濃度是否異常，進而在疾病發生初期早期診斷並早期治療已是目前的趨勢。本實驗設計ㄧ磁振造影對比劑[Gd(DO3A-CF3)]，希望利用順磁性鑭系金屬-釓(III)與氟原子之間的paramagnetic relaxation enhancement ( PRE ) effect，使19F MRI訊號被遮蔽，並在偵測到過氧亞硝酸根陰離子後，因官能基斷裂造成釓金屬與氟原子距離改變，使19F MRI訊號顯露。本研究將對此磁振造影對比劑[Gd(DO3A-CF3)]的合成做深入研究與探討，其中trifluoro ketone官能基的強拉電子能力是造成合成不易的主因。另外，我們以合成出的其中一個化合物4-(4-(3-bromopropoxy)phenyl)-1,1,1trifluorobutan-2-one (4) 與過氧亞硝酸根陰離子進行反應，得到預期的切割片斷，並以19F NMR的化學位移證明[Gd(DO3A-CF3)]具有偵測過氧亞硝酸根陰離子的可行性。

In the past ten years, lots of research indicated that it has high relativity between peroxynitrite and the diseases like septic shock, cancer, neurodegenerative disease, and inflammation, etc. It’s become a trend to discover the disease earlier before it gets too late. We have developed a new contrast agent [Gd(DO3A-CF3)] that can detect peroxynitrite by 19F MRI. In this article, we will discuss two synthetic routes about the 19F MRI contrast agent: [Gd(DO3A-CF3)]. We even try to detect peroxynitrite by 4-(4-(3-bromopropoxy)phenyl)-1,1,1-trifluorobutan-2-one(4), and with this successful result, we still keep on trying to synthesize [Gd(DO3A-CF3)].