Development of Novel Molecular Imaging Agents and Methods for Magnetic Resonance Imaging

新型分子成像剂和磁共振成像方法的开发

• 批准号: RGPIN-2017-06338
• 负责人: Scholl, Timothy
• 金额: $ 1.82万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680508
• 关键词: Development; Novel; Molecular; Imaging; Agents

The central goal of this research is the development of molecular imaging methods and agents for use with magnetic resonance imaging (MRI). Molecular imaging is a research discipline, which seeks to non-invasively visualize, characterize and quantify processes taking place at the molecular or cellular level in living organisms. Since MRI is already the standard of care in many diseases, there is great interest in developing new agents and methods for MRI to image molecular processes in vivo. MRI produces excellent images of tissue with high contrast and resolution. It is also capable of providing “functional” information, which can provide important context for understanding molecular imaging data. Unfortunately it is often difficult to detect molecular “targets” using MRI due to their low in vivo concentration and the limited sensitivity of MRI. The research proposed in this Discovery Grant is focused on developing new molecular imaging agents and methods with high target sensitivity and specificity for use with MRI. There are three general research objectives to support this research goal.*** Our first research objective is the characterization of new contrast agents using relaxometry. Many contrast agents for MRI are based on paramagnetic compounds, which increase the relaxation of nearby tissue. The effectiveness of these agents is characterized by their relaxivity. This is measured in a series of experiments known as Nuclear Magnetic Relaxation Dispersion (NMRD) measurements. We will collaborate with contrast agent chemistry groups developing new MRI agents, providing them NMRD data, which can be used to engineer next-generation agents. In addition, we are developing a fast magnetic field-cycling method for MRI known as dreMR, which can be used to improve the “specificity” of targeted contrast agents for molecular imaging.***In addition to protons, other nuclei can be used with MRI to determine important information about the cellular environment. We are interested in in vivo imaging of sodium and carbon-13 nuclei with MRI, which can reveal important information about biochemical processes in cells. This requires development of special software (known as pulse sequences) and RF hardware for MRI. Efficient pulse sequences and RF hardware will increase the sensitivity of MRI so that we can reduce our image acquisition time and improve the spatial resolution of our images. *** Our final objective is the development of a reporter-gene and probe system for magnetic resonance and bioluminescence imaging modalities. MRI reporter/probe systems can be used for tracking the location and fate of implanted cells. MRI reporters have excellent image resolution and tissue penetration but lack sensitivity compared to bioluminescence reporters. We will use genome-editing methods to add sensitive BLI and MRI reporter genes to cell lines, which will enable improved cell tracking experiments in animals.

本研究的中心目标是开发用于磁共振成像（MRI）的分子成像方法和试剂。分子成像是一门研究学科，旨在非侵入性地可视化，表征和量化生物体中分子或细胞水平上发生的过程。由于MRI已经是许多疾病的护理标准，因此人们对开发用于MRI的新试剂和方法以在体内成像分子过程非常感兴趣。MRI可产生高对比度和高分辨率的组织图像。它还能够提供“功能”信息，这可以为理解分子成像数据提供重要的背景。不幸的是，由于分子在体内的浓度低和MRI的灵敏度有限，使用MRI检测分子“靶标”通常是困难的。这项发现补助金中提出的研究重点是开发新的分子成像剂和方法，具有高靶向灵敏度和特异性，可用于MRI。有三个一般的研究目标来支持这一研究目标。 我们的第一个研究目标是使用弛豫法表征新的造影剂。用于MRI的许多造影剂基于顺磁性化合物，其增加附近组织的松弛。这些药剂的有效性的特征在于它们的弛豫性。这是在一系列被称为核磁弛豫色散（NMR）测量的实验中测量的。我们将与造影剂化学小组合作开发新的MRI试剂，为他们提供可用于设计下一代试剂的NMRD数据。此外，我们正在开发一种用于MRI的快速磁场循环方法，称为dreMR，可用于提高分子成像靶向造影剂的“特异性”。除了质子，其他核可以与MRI一起使用，以确定有关细胞环境的重要信息。我们感兴趣的是在体内成像的钠和碳-13核与MRI，它可以揭示有关细胞中的生化过程的重要信息。这需要开发用于MRI的特殊软件（称为脉冲序列）和RF硬件。高效的脉冲序列和RF硬件将提高MRI的灵敏度，从而减少图像采集时间并提高图像的空间分辨率。*** 我们的最终目标是开发一种用于磁共振和生物发光成像的基因和探针系统。MRI报告/探针系统可用于跟踪植入细胞的位置和命运。MRI报告子具有优异的图像分辨率和组织穿透性，但与生物发光报告子相比缺乏灵敏度。我们将使用基因组编辑方法将敏感的BLI和MRI报告基因添加到细胞系中，这将改善动物细胞跟踪实验。