一种高稳定性钆类核磁共振成像造影剂的合成  

Synthesis of a Highly Stable Gadolinium Based MRI Contrast Agent

作　　者：程丽坤[1] 钱伟桥 丁云 胡爱国[1] CHENG Li-kun;QIAN Wei-qiao;DING Yun;HU Ai-guo(Shanghai Key Laboratory of Advanced Polymeric Materials,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学材料科学与工程学院,上海市先进聚合物材料重点实验室,上海200237

出　　处：《华东理工大学学报（自然科学版）》2018年第2期168-174,共7页Journal of East China University of Science and Technology

基　　金：国家自然科学基金(21274042)

摘　　要：合成了一种基于氮氧化二乙烯三胺五乙酸(DTPA)二异丙胺双酰胺的钆配合物,兼具高弛豫率和高稳定性。通过高分辨质谱、核磁谱图确认了氮氧化配体及对应的钆配合物的结构,并通过电位滴定法测得其配位稳定性常数。实验结果表明此配合物的水合常数为3,弛豫率(16.39mM^(-1)·s^(-1))达到商用造影剂的3倍,稳定性优于商用造影剂Gd-DTPA-BMA(Omniscan~)且表现出良好的成像效果以及优异的生物相容性,具有投入临床应用的巨大潜力。Magnetic Resonance Imaging(MRI)is a powerful method for clinical diagnosis and therapy due to the distinguishing characteristics of providing high-quality three-dimensional images of soft tissue without the need for harmful ionizing radiation.Complexes of gadolinium(Ⅲ)have proven to be especially effective MRI contrast agents,as it is estimated that they are needed for over 30%of the patients to accelerate relaxation rate of in vivo water protons,thus enhancing the contrast of different biological tissues and definition between normal tissues and diseased parts.For more sensitive small-molecule gadolinium-based MRI contrast agents,one essential requirement is to increase the hydration number q,which enhances the gadolinium’s relaxivity.However,with the concern of chronic kidney disease(CKD)and nephrogenic systemic fibrosis(NSF),competition between strong chelate stability and free water coordination sites has increasingly become a challenge to MRI enhancement agent design.A highly stable N-oxide-DTPA-bisamide-based Gd(Ⅲ)complex with 3 coordinated water molecules is synthesized.The general methods such as 1H-NMR,13 C-NMR and ESI-MS spectroscopy are used to characterize the structures of the ligand and the complex.The hydration number determined by the fluorescence lifetime of its Europium(Ⅲ)analogue is 3.MRI measurement shows much higher relaxivity value(16.39 mM-1·s-1)than commercial contrast agents.By fitting the potentiometric data with HYPERQUAD program,the formation constants of the Gd(Ⅲ)complex are calculated and demonstrated a superior stability over Gd-DTPA-BMA(Omniscan).Meanwhile,in vivo imaging shows good imaging quality and cell tests reveal low cytotoxicity of the complexes,which indicate its great potential for future clinical applications.

关 键 词：核磁共振成像造影剂 氮氧化 水合常数 弛豫率 稳定性 

分 类 号：O621.3[理学—有机化学]