Parahydrogen-induced hyperpolarization of 13C labeled keto carboxylic acids for medical applications: synthesis, polarization transfer, 13C-MRI

仲氢诱导的 13C 标记酮羧酸超极化用于医疗应用：合成、极化转移、13C-MRI

• 批准号: 527469039
• 负责人: Professor Dr. Rainer Herges
• 金额: --
• 依托单位: Otto Diels - Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/527469039?language=en
• 关键词: Parahydrogen; induced; hyperpolarization; 13C; labeled

Arguably the most critical 3D imaging modalities in medicine are MRI and CT. MRI is gaining importance because it does not use ionizing radiation, and it allows visualization beyond just anatomic or structural imaging. Anomalies in metabolic processes are often reliable indicators of diseases at very early stages of illness before anatomical changes (e.g., tumors) are visible in structural imaging. However, MRI is notoriously insensitive, and metabolic imaging requires even higher signal-to-noise ratios than mere anatomical imaging. Hyperpolarization to date is probably the most promising approach to increase the sensitivity of NMR and MRI to a level where intermediates in metabolic pathways can be detected, and their concentration visualized with spatial resolution. Among a plethora of biomarkers, α-ketocarboxylic acids are key molecules because they are intermediates in energy metabolism pathways such as the citric acid cycle and glycolysis. Particularly the pyruvate/lactate conversion is known to be an instrumental indicator for early-stage cancer (Warburg effect). The ultimate goal of this research project is to provide the scientific and technological basis for in vivo molecular and metabolic imaging by MRI using the so-called parahydrogen-induced polarization (PHIP) method. Towards this end, we will develop a cost-efficient synthesis of 13C and 2H labeled vinyl esters of pyruvate and other derivates of α-ketocarboxylic acids as precursors for PHIP (goal 1), and we will design hardware and PHIP experiments in intermediate magnetic fields for the scalable and convenient production of pyruvate and other α-ketocarboxylic acids for 13C MRI (goal 2). In vivo experiments will be performed in collaboration with other groups independently from this project.

可以说，医学中最关键的3D成像模式是MRI和CT。MRI越来越重要，因为它不使用电离辐射，并且它允许可视化而不仅仅是解剖或结构成像。 代谢过程中的异常通常是疾病在解剖学变化之前的非常早期阶段的可靠指标（例如，肿瘤）在结构成像中可见。然而，MRI是出了名的不敏感，并且代谢成像需要比仅仅解剖成像更高的信噪比。迄今为止，超极化可能是最有前途的方法，以增加NMR和MRI的灵敏度，代谢途径中的中间体可以检测到的水平，其浓度可视化的空间分辨率。在众多生物标志物中，α-酮基羧酸是关键分子，因为它们是能量代谢途径（如柠檬酸循环和糖酵解）的中间体。特别地，已知丙酮酸/乳酸转化是早期癌症的工具性指标（瓦尔堡效应）。本研究项目的最终目标是为使用所谓的仲氢诱导极化（PHIP）方法通过MRI进行体内分子和代谢成像提供科学和技术基础。为此，我们将开发一种具有成本效益的13 C和2 H标记的丙酮酸乙烯酯和其他α-酮基羧酸衍生物的合成方法，作为PHIP的前体（目标1），我们将设计中间磁场中的硬件和PHIP实验，用于13 C MRI的丙酮酸和其他α-酮基羧酸的可扩展和方便的生产（目标2）。体内实验将与独立于该项目的其他小组合作进行。