磁共振造影剂能够缩短质子的弛豫时间，改变质子产生的信号强度，从而提高人体正常与病态组织的成像对比度，更好地对病变组织进行诊断。目前临床使用的造影剂存在的问题主要是使用剂量大，灵敏度低，不具备靶向性，因此亟需研发新型磁共振造影剂来改善此类现象。本项目致力于研究新型镧系金属高分子磁共振造影剂及其在生物医学领域的应用。利用分子设计方法，将金属结合水与外界水交换速率控制在10^4-10^7/s之间，此时的造影剂较适用于T2ex体系。此项目中，首先设计一系列小分子T2ex类造影剂，研究小分子造影剂的水分子交换速率对弛豫率的影响；其次通过合成高分子T2ex类造影剂来增加其弛豫率、灵敏度以及在血液中的循环时间，来探索其在癌症组织中的成像效果；最后还将合成T2ex类的靶向型高分子造影剂，探索其在动物体内的靶向性及成像效果。这对新型磁共振造影剂的设计、合成及其在生物成像等领域的应用具有重要的理论与实际意义。

Water exchange rate is one of the most important parameter when design the lanthanide-based MRI contrast agent. Once the lanthanide-based contrast agent has the water exchange rate in the range of 10^4 to 10^7 s, this type agent is not only suitable for T2ex type MRI agent, but also could be used as CEST agent. In this grant, we will focus on synthesis and applications of T2ex molecules that has an inner-sphere water exchange site thereby increase the line-broadening of bulk water signal. We will demonstrate the utility of these new polymer agents for imaging common hallmarks of cancer in vitro and in vivo before the end of the next 3-year grant cycle. If successful, the agents developed in this project will make MRI competitive as an effective molecular imaging tool for cancer diagnosis..Aim 1: we aim to synthesis T2ex type polymer-based MRI contrast agent to explore the possibility for further in-vivo imaging due to the higher transverse relaxivity, sensitivity and longer blood circulation time. .Aim 2: we propose to synthesis RDG and Folic acid T2ex based polymeric MRI contrast agent for image specific tumor tissue.