Hyperpolarized 15N contrast agents for the detection of copper and zinc ions

用于检测铜离子和锌离子的超极化 15N 造影剂

• 批准号: 491827624
• 负责人: Dr. Stefan Glöggler
• 金额: --
• 依托单位: Forschungsgruppe NMR-Signalverstärkung
• 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/491827624?language=en
• 关键词: Hyperpolarized; 15N; contrast; agents; detection

The causes of many diseases, such as neurodegenerative processes,are associated with increased concentrations of metal ions. Important representatives of these ions are copper and zinc. The detection of endogenous ions can be accomplished by magnetic resonance imaging (MRI). However, MRI has its limitations because it is an intrinsically insensitive method. To increase the sensitivity of MRI, the method of hyperpolarization was introduced which increases the signals of contrast agents by more than 10,000 times. I am planning to use this method for the development of new, sensitive contrast agents, which will allow for the detection of copper and zinc ions in 100 micromolar concentrations, as they are often found in pathologies. I am going to use the approach to hyperpolarize nitrogenspins (15N) in new, to be developed contrast agents. The 15N-species will have a very long lifetime and will be traceable for more than 10 minutes. This corresponds to one order of magnitude longer traceability than with 13C-labeled compounds, which are used as standard in hyperpolarization studies. The newly designed contrast agents will be optimized with respect to their magnetic resonance parameters and finally tested in in vitro imaging experiments. At the end of the project, the new hyperpolarized contrast agents will be developed to the point where preclinical studies in disease models can follow.

许多疾病的原因，如神经退行性过程，都与金属离子浓度增加有关。这些离子的重要代表是铜和锌。内源性离子的检测可以通过磁共振成像（MRI）来完成。然而，MRI有其局限性，因为它本质上是一种不敏感的方法。为了提高MRI的灵敏度，引入了超极化方法，该方法将造影剂的信号增加了10，000倍以上。我计划使用这种方法开发新的，灵敏的造影剂，这将允许检测铜和锌离子在100微摩尔浓度，因为它们经常在病理学中发现。我将在新的待开发的造影剂中使用高浓度氮自旋（15 N）的方法。15 N-物种将具有非常长的寿命，并且将可追溯超过10分钟。这相当于比13 C标记的化合物长一个数量级的可追溯性，13 C标记的化合物在超极化研究中用作标准。新设计的造影剂将根据其磁共振参数进行优化，并最终在体外成像实验中进行测试。在项目结束时，新的超极化造影剂将被开发到疾病模型的临床前研究可以遵循的程度。