Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso

超高场强（e7 T）磁共振对阳性造影剂的需求很大 成像（MRI），以提高空间分辨率和对临床前和 临床研究我们的长期目标是开发用于超高场强MRI的阳性对比剂， 通过关注EuII复合物，这是诊断医学中最有前途的领域之一， study.本申请的总体目标是建立必要的基础翻译我们的 通过最大化稳定性，优化成像性能， 并评估毒性。支持拟议研究的基本原理是EuII可以稳定 通过配体修饰和与抗氧化剂一起配制， 正如我们最近所展示的。这一建议的预期成果是建立基于欧盟II的 在超高场强MRI中用作造影剂的复合物。预计这一结果将产生一个 积极的影响，有助于国家卫生研究院的使命在人类疾病的诊断。我们计划实现 通过追求三个具体目标来实现该提案的目标：（1）化学增强稳定性， 我们的含EuII的配合物的成像相关参数;（2）表征我们的EuII的毒性， 含Eu Ⅱ的配合物;和（3）表征我们的含Eu Ⅱ的配合物的体内成像性质。 新的基于EuII的探针将是重要的，因为它们有望使诊断图像， 在超高场强下采集，分辨率更高，比目前在临床上采集的时间更短 磁场强度此外，由于超高场强在NIH支持的临床前研究中很常见， 研究，这项建议预计将最大限度地提高回报，在许多其他投资的国家卫生研究院有关， 核磁共振

There is a great need for positive contrast agents for ultra-high field strength (e7 T) magnetic resonance imaging (MRI) to enable increased spatial resolution and sensitivity to disease states in both preclinical and clinical research. Our long-term goal is to develop positive contrast agents for ultra-high field strength MRI to fill this void in diagnostic medicine by focusing on EuII complexes that are among the most promising areas of study. The overall objective of this application is to establish the groundwork necessary for translation of our new EuII-based complexes into useful contrast agents by maximizing stability, optimizing imaging properties, and evaluating toxicity. The rationale that underpins the proposed research is that EuII can be stabilized against oxidation and rendered non-toxic in vivo through ligand modification and formulation with antioxidants as we have recently demonstrated. The expected outcome of this proposal is the establishment of EuII-based complexes for use as contrast agents in ultra-high field strength MRI. This outcome is expected to have a positive impact by contributing to the NIH's mission in the diagnosis of human diseases. We plan to achieve the objective of the proposal by pursuing three specific aims: (1) to chemically enhance the stabilities and imaging-relevant parameters of our EuII-containing complexes; (2) to characterize the toxicity of our EuII- containing complexes; and (3) to characterize the in vivo imaging properties of our EuII-containing complexes. The new EuII-based probes will be significant because they are expected to enable diagnostic images to be acquired at ultra-high field strengths with higher resolution in less time than those currently acquired at clinical field strengths. Furthermore, because ultra-high field strengths are commonplace in NIH-supported preclinical research, this proposal is expected to maximize returns in the many other investments of the NIH related to MRI.