Production of biocompatible 13C-hyperpolarized metabolic contrast agents at a gas-solid-interface

核磁共振（NMR）是一种广泛应用于医学成像以提高诊断能力的现象。然而，灵敏度在许多应用中是有限的。增强核磁共振信号的一种可能性是使用超极化代谢物作为造影剂。因此，核自旋态在代谢物中被选择性地过度填充，导致比正常/热信号强4个数量级以上的增强信号。随后在体内注射超极化代谢物，并允许实时检测例如肿瘤代谢。由于健康组织和恶性组织的代谢行为不同，可以指导临床诊断。然而，目前，由于极化装置的购置和维护成本高，许多卫生保健和研究机构无法获得进行这些调查的技术。在本提案中，我们计划研究一种成本效益高的替代方案，可以使用对氢生成生物相容性超极化造影剂。通过加氢作用，对氢自旋顺序在代谢物前体中转化为可观察到的磁化，导致这些前体中的强信号增强。随后的化学反应将前体迅速转化为可用作造影剂的所需代谢物。氢化通常使用均相催化剂，在实验的时间尺度上很难从代谢物溶液中去除，导致毒性问题。在这里，我们计划研究合适的代谢物前驱体在气固界面的加氢，产生气态超极化前驱体，这些前驱体将被捕获在水中并转化为最终代谢物。我们将使用固体纳米催化剂来促进气固界面的氢化，因此我们将实现催化剂和被捕获的造影剂之间的空间分离。这将减轻对毒性的担忧。在细胞实验中，我们将证明获得的代谢物（特别是醋酸盐、乳酸盐和丙酮酸盐）被代谢。由于超极化代谢物的快速产生，我们将能够检测到细胞中的代谢变化，这些变化可以实时触发。最终，通过我们提出的技术，我们将为检测和研究代谢过程铺平新的途径。

Nuclear Magnetic Resonance (NMR) is a phenomenon which is widely used e.g. in medical imaging to improve diagnostic capabilities. Sensitivity, however, is limiting in many applications. One possibility to enhance NMR signals is to use hyperpolarized metabolites as contrast agents. Thereby, nuclear spin states are selectively overpopulated in metabolites, leading to enhanced signals that are more than four orders of magnitudes more intense than the normal/thermal signal. Hyperpolarized metabolites are subsequently injected in vivo and allow for the real-time detection of e.g. a tumor metabolism. As the metabolic behavior is different between healthy and malicious tissue, this can guide clinical diagnosis.Currently, techniques to perform these investigations, however, are out of reach for many health care and research institutions, due to high acquisition and maintenance costs for polarization setups. In this proposal we are planning to investigate a cost-efficient alternative with which biocompatible hyperpolarized contrast agents can be generated using para-hydrogen. Via hydrogenation, the para-hydrogen spin order is converted into observable magnetization in metabolite precursors, leading to strong signal enhancement in these precursors. A subsequent chemical reaction rapidly converts the precursor into the desired metabolite that can be utilized as contrast agent. The hydrogenation usually utilizes homogeneous catalysts that can hardly be removed from the metabolite solutions on the timescale of the experiment, leading to toxicity concerns. Here, we are planning to investigate the hydrogenation of suitable metabolite precursors at a gas-solid-interface, which yield gaseous hyperpolarized precursors that will be trapped in water and converted into the final metabolites. We are going to use solid nano-catalysts that promote the hydrogenation at the gas-solid-interface and we will therefore achieve a spatial separation between the catalyst and the trapped contrast agents. This will mitigate toxicity concerns. In cell experiments, we will show that the metabolites obtained (specifically acetate, lactate and pyruvate) become metabolized. Due to the rapid production of hyperpolarized metabolites, we will be able to detect metabolic changes in the cells that can be triggered at-will in real-time. Ultimately, with our proposed technique we will pave new pathways to detect and investigate metabolic processes.