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

先进Eu(II)基超高场磁共振造影剂的研究

• 批准号: 8628271
• 负责人: MATTHEW J ALLEN
• 金额: $ 32.54万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628271
• 关键词: Air; Antioxidants; Area; Biodistribution; Biological Assay; Brain; Brain imaging; Charge; Chemical Structure; Chemicals; Clinical; Clinical Research; Complex; Contrast Media; Coupled; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Disease; Drug Formulations; Drug-sensitive; Early Diagnosis; Foundations; Future; Goals; Health; Heart Diseases; Hemoglobin; Housing; Image; In Vitro; Investments; Kinetics; Lead; Ligands; Magnetic Resonance Imaging; Malignant Neoplasms; Maximum Tolerated Dose; Measurement; Medicine; Mission; Modification; Molecular; Monitor; Outcome; Patients; Pattern; Property; Public Health; Relative (related person); Research; Research Proposals; Resolution; Rheumatoid Arthritis; Scanning; Series; Stroke; Structure-Activity Relationship; Therapeutic; Time; Toxic effect; Translating; Translations; Traumatic Brain Injury; United States National Institutes of Health; base; disease diagnosis; effective therapy; functional group; human disease; improved; in vivo; in vivo imaging; innovation; magnetic field; meetings; oxidation; planetary Atmosphere; pre-clinical research; public health relevance; success; tool

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.

超高场强（e7 T）磁共振非常需要阳性造影剂 成像（MRI），以提高临床前和疾病状态的空间分辨率和敏感性 临床研究。我们的长期目标是开发用于超高场强MRI的阳性造影剂，以填补 通过关注EuII复合物来弥补诊断医学中的这一空白，EuII复合物是最有前途的领域之一 学习。该应用程序的总体目标是为翻译我们的内容奠定必要的基础。 通过最大限度地提高稳定性、优化成像特性，将新的基于 EuII 的复合物转化为有用的造影剂， 并评价毒性。支持该研究的基本原理是 EuII 可以稳定 通过配体修饰和抗氧化剂配方，抗氧化并使其在体内无毒 正如我们最近所证明的那样。该提案的预期成果是建立基于EuII的 用作超高场强 MRI 造影剂的复合物。这一结果预计将有 通过为 NIH 诊断人类疾病的使命做出贡献，产生积极影响。我们计划实现 该提案的目标是通过追求三个具体目标：（1）从化学上增强稳定性和 我们的含 EuII 复合物的成像相关参数； (2) 表征我们的EuII-的毒性 含有复合物； (3) 表征我们的含 EuII 复合物的体内成像特性。 新的基于 EuII 的探针将具有重要意义，因为它们有望使诊断图像成为可能。 与目前在临床上获得的结果相比，在超高场强下获得的结果在更短的时间内具有更高的分辨率 场强。此外，由于超高场强在 NIH 支持的临床前研究中很常见 研究表明，该提案预计将最大限度地提高 NIH 与以下领域相关的其他许多投资的回报： 核磁共振成像。