Contrast Agents & Radiotracers As Activity-Based Sensors of Faulty Metabolism

在我们从健康到生病的过程中，想象我们身体深处的生化变化的能力已经彻底改变了我们对疾病的理解。化学和物理方面的创新结合在一起，促成了这场革命，推动了生成这些图像所需的机器和可注射化学探测器的发展。继续提高我们的成像能力的一种方法是通过新的化学方法以新的方式控制这些成像系统的物理属性。目前的提议将产生新的化学方法，允许通过磁共振成像同时跟踪多个生化目标。还将开发新的纳米颗粒组件，这些组件将操纵光线，允许使用光学相干断层扫描来评估我们血管的生物化学。另一种提升我们成像能力的方法是重新思考我们如何选择我们的成像。选择在很大程度上采取了简约主义的方法(例如，一种蛋白质的表达水平)，落后于平行的生物化学领域。基于系统的方法的价值已经在生物化学中被接受，它着眼于动态生化事件的净结果来定义细胞或组织的健康。为此，我们将开发一种新的显像剂来报告使用维生素B6的这一“净结果”，维生素B6是140多个生化反应的基本促进剂。总体而言，这项拟议的工作旨在通过新的化学方法扩展成像的功能，并重新定义成像生物标记物的价值构成。这项提议的结果将在短期内影响成像科学和我们对疾病的分子理解。新的化学平台将使全球的成像化学家和生物化学家能够评估一组以前不可能实现的生化目标。疾病过程是协调一致的生化途径的净结果，所提出的化学将使关于蛋白质在空间和时间上相互作用的关键信息变得独特。从长远来看，这些用于成像探针开发的化学平台可能会对临床成像产生影响，因为这里针对的所有成像方法都是每天在人类身上使用的。因此，拟议的工作可能会对基于成像的诊断产生积极影响，并改善加拿大人的健康。重要的是，拟议的培训计划还将在克服将代表性不足的群体纳入科学界的障碍方面取得进展。通过渥太华与支持渥太华因纽特家庭的当地社区组织之间的伙伴关系，我们将开展科学宣传，为因纽特青年提供与因纽特文化相关的广泛科学规划。

The ability to image the biochemical changes deep inside our bodies as we progress from being healthy to being sick has revolutionized our understanding of disease. The combination of innovations in chemistry and physics has enabled this revolution, advancing both the machines and injectable chemical probes required to generate these images. One way to continue to advance our imaging capabilities is through novel chemistry controlling the physical properties of these imaging systems in new ways. The current proposal will generate new chemical approaches allowing multiple biochemical targets to be tracked at one time by Magnetic Resonance Imaging. New assemblies of nanoparticles that will manipulate light to allow the biochemistry of our blood vessels to be evaluated using Optical Coherence Tomography will also be developed. Another way to advance our imaging capabilities is to rethink how we pick what we image. Selection has largely taken a reductionist approach (e.g. expression levels of one protein), falling behind paralleled fields of biochemistry. The value of a systems-based approach has been accepted in biochemistry, which looks at the net outcome of dynamic biochemical events to define the health of the cell or tissue. To this end, we will develop a new imaging agent to report on this `net outcome' for the use of Vitamin B6, an essential enabler of more than 140 biochemical reactions. Overall, the proposed work seeks to expand the functionality of imaging with new chemical approaches, and to redefine what constitutes value in an imaging biomarker. The outcomes of this proposal are positioned to impact imaging science and our molecular understanding of disease in the short-term. New chemical platforms will enable imaging chemists and biochemists globally to evaluate of sets of biochemical targets not previously possible. Disease processes are the net outcomes of concerted biochemical pathways, and the chemistry proposed would make key information about the interaction of proteins in space and time uniquely accessible. In the longer-term, these chemical platforms for imaging probe development can have impact on clinical imaging, as all of the imaging approaches targeted herein are used daily on humans. As a result, the proposed work could positively impact imaging-based diagnostics and improve the health of Canadians. Importantly, the proposed training program will also make strides to overcome barriers to the inclusion of under-represented groups in science. With a partnership between uOttawa and a local community organization supporting Inuit families in Ottawa, we will develop science outreach providing a broad range of scientific programming tied to Inuit culture for Inuit youth.