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

描述(申请人提供)：在临床前和临床研究中，非常需要用于超高场强(E7T)磁共振成像(MRI)的阳性造影剂，以提高空间分辨率和对疾病状态的敏感性。我们的长期目标是开发用于超高场强MRI的阳性造影剂，通过专注于EuII复合体来填补诊断医学中的空白，EuII复合体是最有前途的研究领域之一。这项应用的总体目标是通过最大化稳定性、优化成像性能和评估毒性，为将我们新的基于EuII的络合物转化为有用的造影剂奠定必要的基础。支持这项拟议研究的基本原理是，正如我们最近所证明的那样，通过配体修饰和抗氧化剂配方，EuII可以在体内稳定抗氧化并呈现无毒状态。这项提议的预期结果是建立基于EuII的复合体，用作超高场强磁共振成像的造影剂。这一结果预计将对美国国立卫生研究院诊断人类疾病的使命产生积极影响。我们计划通过追求三个具体目标来实现该提案的目标：(1)从化学上提高我们的含EuII的络合物的稳定性和成像相关参数；(2)表征我们的含EuII的络合物的毒性；以及(3)表征我们的含EuII的络合物的体内成像特性。新的基于EuII的探头将具有重要意义，因为它们有望以超高场强和更高的分辨率在更短的时间内获得诊断图像，而不是目前在临床现场获得的图像 强项。此外，由于超高场强在NIH支持的临床前研究中很常见，这一建议有望使NIH与MRI相关的许多其他投资获得最大回报。

DESCRIPTION (provided by applicant): 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 voi 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.