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: 9043062
• 负责人: MATTHEW J ALLEN
• 金额: $ 33.6万
• 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/9043062
• 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-sensitive; Early Diagnosis; Formulation; 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; 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; contrast enhanced; disease diagnosis; effective therapy; functional group; human disease; improved; in vivo; in vivo imaging; innovation; magnetic field; meetings; oxidation; planetary Atmosphere; pre-clinical research; success; systemic toxicity; tool

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.

描述（由申请人提供）：非常需要用于超高场强（e7 T）磁共振成像（MRI）的阳性造影剂，以提高临床前和临床研究中对疾病状态的空间分辨率和灵敏度。我们的长期目标是开发用于超高场强MRI的阳性造影剂，以填补诊断医学中的这一空缺，重点关注EuII复合物，这是最有前途的研究领域之一。本申请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，建立将我们的新的基于Eu II的复合物转化为有用的造影剂所需的基础。支持拟议的研究的基本原理是，EuII可以稳定抗氧化，并通过配体修饰和抗氧化剂的配方在体内无毒，因为我们最近已经证明。该提案的预期结果是建立基于Eu II的复合物，用作超高场强MRI中的造影剂。这一结果有望通过促进NIH在人类疾病诊断方面的使命而产生积极影响。我们计划通过追求三个具体目标来实现该提案的目标：（1）化学增强我们的含Eu II的络合物的稳定性和成像相关参数;（2）表征我们的含Eu II的络合物的毒性;和（3）表征我们的含Eu II的络合物的体内成像性质。新的EuII探针将是重要的，因为它们有望使诊断图像能够在超高场强下以更高的分辨率在比目前在临床领域获得的更短的时间内获得 长处.此外，由于超高场强在NIH支持的临床前研究中很常见，因此该提案有望使NIH与MRI相关的许多其他投资的回报最大化。