多核鑭系釓錯合物作為磁振顯影劑之性質探討

Abstract

本人近年來在大環 macrocyclic aminopolycarboxylate ligands 金屬錯合物 (例如DO2A，NO2A 和衍生物)的許多研究中發現在錯合的過程中因為電價、時 間、酸鹼、濃度等因素而有可能造成雙核或多核的化合物，進而造成顯影能力或 DNA/RNA 切割能力的改變。所以在未來的計劃裡我們準備直接合成新的釓 (Gadolinium(III))多核(polynuclear)磁振(Magnetic Resonance Imaging, MRI)對 比顯影劑，以及其他含醚基雜環配位子之釓錯合物，以為比較，並針對安全性和 成像效力、熱力學的穩定度(Thermodynamic stability)、動力學的安定性行 (Kinetic lability)、和relaxivity 作深入之探討。研究計畫將為polynuclear Gd(III) chelates 發展合成方法學，並且利用UV、雷射螢光(laser excitation fluorescence, use Eu(III) chelates)、NMR、分子模擬等方法更進一步探索要在 此類對比顯影劑在水溶液之結構及生成過程，以及其動態特性，進而瞭解並設計 更新及有效之對比顯影劑。

In this research, we will study the effects of pH, lanthanide metal ionic radii, number of inner-sphere coordinated water molecules, structure, and charge on the dinuclear and/or polynuclear formation of lanthanide complexes of macrocyclic aminopolycarboxylate ligands such as DO2A and NO2A and their structural analogues, particularly on gadolinium(III) complexes and their applications as magnetic resonance imaging (MRI) contrast agents. It is highly possible that dimeric or higher-order gadolinium(III) complexes of DO2A and NO2A are formed at high pH. The formation equilibrium and kinetics of the hydroxo-bridged trivalent lanthanide complexes such as gadolinium(III) complexes has never been studied and is very important to understand their solution behaviors and for biomedical applications such as serving as MRI contrast agents. This proposal will develop synthetic procedures for dimeric gadolinium(III) chelates of macrocyclic aminopolycarboxylate ligands (e.g. DO2A, NO2A, and derivatives). These newly prepared potential MRI contrast agents will be characterized by published physical/analytical methods to evaluate thermodynamic stability, kinetic lability, and relaxivity as well as pre-clinical safety and imaging efficacy.