Development of Advanced Molecular Imaging Probes and Contrasts for Magnetic Resonance Imaging

分子成像是一种用于可视化活体细胞功能的非侵入性工具。 对于磁共振成像 (MRI)，通过将造影剂注射到生物体中来对细胞功能进行成像，该造影剂在图像中产生可量化的变化，反映代谢功能的变化。 这些化合物可以设计为优先与特定蛋白质结合或直接被细胞代谢，以便可以使用 MRI 对它们的生物分布的影响进行成像。 与其他成像方式相比，MRI 的固有敏感性较低，面临的挑战是生产在较低浓度下有效的新型造影剂。 影响灵敏度的主要特性是造影剂的“弛豫度”——造影剂通过增加附近组织的磁弛豫而引起信号增强的有效性。 当靶向造影剂处于结合状态时，其弛豫率大大增强，并且其弛豫率高度依赖于磁场。 这一特性被用于一种新型的 MRI 造影剂中，我们开发了这种造影剂，称为 dreMR，通过产生与仅结合剂的浓度成比例的造影剂，大大提高了有效目标特异性。 我们还在研究一种基于超极化富含 13C 的内源性化合物的新型药物的松弛作用。 这些缓慢松弛的试剂在体外被高度磁化（超极化），然后被注射到动物模型中，并与其代谢产物一起进行光谱成像。 代谢物的空间分布提供了有关体内细胞过程的有价值的信息。 该发现补助金的目标有三个：1) 测量合作化学小组生产的新型造影剂的弛豫曲线，2) 改进 dreMR 方法并将其扩展到动物模型的体内成像，3) 确定富含 13C 的化合物的超极化状态的“衰减时间”以及添加顺磁化合物以增强超极化的效果。 这笔赠款将在研究项目的每年期间为一名医学物理学本科生和两名研究生提供 MRI 科学培训。

Molecular imaging is a non-invasive tool for visualization of cellular function in living organisms. For magnetic resonance imaging (MRI), cellular function is imaged by injecting a contrast agent into an organism that produces quantifiable changes in the image reflecting variations in metabolic function. These compounds may be designed to bind preferentially to a specific protein or be metabolized directly by cells so that the effects of their biodistribution can be imaged using MRI. Compared with other imaging modalities, the intrinsic sensitivity of MRI is low and the challenge is to produce newer contrast agents that can be effective at lower concentrations. The chief property affecting sensitivity is the contrast agent "relaxivity" - the effectiveness of an agent to cause signal enhancement through increased magnetic relaxation of nearby tissue. The relaxivity of targeted contrast agents is greatly enhanced when the agent is in its bound state and its relaxivity is highly dependent on the magnetic field. This characteristic is exploited in a novel form of MRI contrast, which we have developed called dreMR that greatly increases the effective target specificity by producing a contrast that is proportional to the concentration of only bound agent. We are also studying the relaxation of a new type of agent based on hyperpolarized 13C-enriched endogenous compounds. These slowly relaxing agents are highly magnetized (hyperpolarized) in vitro and then are injected into an animal model and spectroscopically imaged along with their metabolic products. The spatial distributions of the metabolites yield valuable information about in vivo cellular processes. The objectives of this Discovery Grant are three-fold: 1) measure relaxivity profiles of novel contrast agents produced by collaborating chemistry groups, 2) improve the dreMR method and extend it to in vivo imaging with animal models, and 3) determine the "decay time" of the hyperpolarization state for 13C-enriched compounds and the effects of adding paramagnetic compounds to enhance hyperpolarization. This grant will provide training in MRI science for one undergraduate and two graduate students in medical physics during each year of the research program.