Novel MRI Probes for In Vivo Molecular Imaging

用于体内分子成像的新型 MRI 探针

• 批准号: 6829593
• 负责人: ALAN C EVANS
• 金额: $ 11.63万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-11 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6829593
• 关键词: bioimaging /biomedical imaging; contrast media; enzyme activity; enzyme inhibitors; glioma; histology; immunocytochemistry; laboratory mouse; laboratory rat; magnetic resonance imaging; metalloendopeptidases; molecular probes; organometallic compounds; pathologic process; technology /technique development

DESCRIPTION (provided by applicant): The ability to non-invasively image molecular targets in vivo using magnetic resonance imaging (MRI) represents a major advance in the field of diagnostic imaging. In this project, we propose to develop novel MRI probes which will allow for imaging of the expression of matrix metalloproteinases (MMPs) in vivo. MMPs are over expressed in many pathological process, including cancer, cardiovascular, inflammatory, and immune diseases. In the central nervous system, MMPs are known to be over expressed in high-grade gliomas and multiple sclerosis (MS). The ability to image the levels of MMPs in vivo will have profound ramifications on cur understanding of these disease process, their response to treatment, and our ability to develop new, more effective pharmacological agents. In Phase I (R21) of this project, we will develop the novel MRI probes and evaluate them on a rat CS glioma model. This phase has three specific aims: Specific Aim #1: Development of a MMP-2 activated permeability modulator. Specific Aim #2: Development of a MMP-2 activated organometallic-based probe. Specific Aim #3: In vivo imaging of MMP-2 expression in a CS glioma model. In Phase II (R33) of this project, we will extend this new technology to study other pathological processes, as well as evaluate the ability of our vascular permeability probe to improve local delivery of pharmacological agents. This phase has three specific aims: Specific Aim #1: In vivo imaging of MMP-2 expression in human tumor xenografts. Specific Aim #2: In vivo imaging of MMP-9 expression in a rat EAE model of MS. Specific Aim #3: Evaluation of the ability of vascular permeability modulator to improve the therapeutic efficacy of pharmacological agents.

描述（由申请人提供）： 使用磁共振成像 (MRI) 对体内分子目标进行非侵入性成像的能力代表了诊断成像领域的重大进步。在这个项目中，我们建议开发新型 MRI 探针，用于对体内基质金属蛋白酶 (MMP) 的表达进行成像。 MMPs在许多病理过程中过度表达，包括癌症、心血管、炎症和免疫疾病。在中枢神经系统中，已知 MMP 在高级神经胶质瘤和多发性硬化症 (MS) 中过度表达。体内 MMP 水平成像的能力将对我们对这些疾病过程的理解、它们对治疗的反应以及我们开发新的、更有效的药物的能力产生深远的影响。 在该项目的第一阶段 (R21)，我们将开发新型 MRI 探针，并在大鼠 CS 神经胶质瘤模型上对其进行评估。这一阶段有三个具体目标： 具体目标#1：开发 MMP-2 激活的通透性调节剂。 具体目标#2：开发 MMP-2 激活的有机金属探针。 具体目标#3：CS 神经胶质瘤模型中 MMP-2 表达的体内成像。 在该项目的第二阶段（R33）中，我们将扩展这项新技术来研究其他病理过程，并评估我们的血管通透性探针改善药物局部输送的能力。这一阶段有三个具体目标： 具体目标#1：人肿瘤异种移植物中 MMP-2 表达的体内成像。 具体目标#2：MS 大鼠 EAE 模型中 MMP-9 表达的体内成像。 具体目标#3：评估血管通透性调节剂提高药物治疗功效的能力。