Synthesis and Evaluation of Eu(II/III) Systems for Imaging Transient Hypoxia

用于瞬时缺氧成像的 Eu(II/III) 体系的合成与评价

• 批准号: 2714591
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2714591
• 关键词: Synthesis; Evaluation; Eu; II; III

The prolific nature of research into oxygen availability in the body is evident from the award of the Nobel Prize in Physiology or Medicine 2019. Hypoxia is where the body or a region of the body is oxygen deficient due to insufficient delivery of oxygen to living cells. It is significant because it is a major indicator of disease. Indeed, hypoxia is observed in various medical conditions such as Alzheimer's, cardiovascular diseases, kidney diseases, hepatic and neurological disorders, arthritis, metabolic diseases, diabetes, reproductive diseases, and cancer. In clinical medicine, there are currently no routine methods of detecting hypoxia, but clearly such technology, which essentially acts as a semi- universal indicator of disease, would be of significant benefit in improving healthcare.Medical imaging is the process of generating an image of the interior of the body and the aim of this project is to make and evaluate chemical compounds, so-called imaging agents, that when administered to the patient enable imaging of hypoxia. The project will focus on europium-containing imaging agents because europium can form stable compounds in two oxidation states i.e. with a different charge on the europium ion, which are both accessible under physiological conditions and exhibit dramatically different magnetic properties and different properties in their interaction with light. This project is based on the hypothesis that the Eu2+ state should be favoured under hypoxic conditions, and the Eu3+ state under non-hypoxic conditions, hence leading to contrast in the generated image, enabling hypoxic tissue to be identified.The ideal properties for a hypoxia sensing technique encompass excellent resolution in the image, non- invasiveness, no oxygen consumption, quantitative measurement of oxygen concentration, and negligible toxicity. Potential modes of imaging hypoxia include Magnetic Resonance Imaging (MRI) which is non-invasive and visualises morphological and functional anatomy with essentially unlimited depth penetration through use of strong magnetic fields and radiofrequency pulses. Utilising MRI would exploit the fact that one of the oxidation states of europium produces positive MRI contrast whereas the oxidation state does not. Another potential hypoxia imaging modality is optical imaging which is also non-invasive and is a powerful tool for visualising subcellular morphologies based on the use of molecules that absorb and emit light. Those that both absorb and emit light are so-called luminescent materials and are particularly useful for imaging as there are fewer chemical species in the body that exhibit luminescence than those that just absorb light, leading to a more defined image. Optical imaging with such europium-containing agents is also likely to produce good contrast because one of the oxidation states of europium displays longer lived luminescence than the other.This project will begin with synthesis of various europium-containing imaging agents and characterisation of their chemical and physical properties and stability, followed by in vitro testing of the agents for MRI and optical imaging of hypoxia and finally in vivo testing of such imaging modalities.This project falls within the EPSRC physical sciences and healthcare technologies research areas.

从2019年诺贝尔生理学或医学奖的获奖可以看出，对体内氧气可用性的研究成果丰富。缺氧是指身体或身体的某一区域由于没有足够的氧气输送到活细胞而缺氧。它之所以重要，是因为它是疾病的主要指标。事实上，在各种疾病中都可以观察到缺氧，如阿尔茨海默氏症、心血管疾病、肾病、肝脏和神经系统疾病、关节炎、代谢疾病、糖尿病、生殖疾病和癌症。在临床医学中，目前还没有检测缺氧的常规方法，但显然，这种技术基本上作为疾病的半通用指标，将对改善医疗保健有重大好处。医学成像是生成人体内部图像的过程，这个项目的目的是制造和评估化合物，即所谓的显像剂，当给病人使用时，可以对缺氧进行成像。该项目将专注于含铕显像剂，因为铕可以在两种氧化状态下形成稳定的化合物，即在铕离子上具有不同的电荷，这两种化合物在生理条件下都可以获得，并且在与光的相互作用中表现出截然不同的磁性和不同的性质。这个项目是基于这样的假设，即在缺氧条件下有利于Eu2+状态，在非缺氧条件下有利于Eu3+状态，从而在生成的图像中产生对比度，从而能够识别缺氧组织。低氧传感技术的理想特性包括图像的高分辨率、非侵入性、无氧消耗、氧浓度的定量测量和可忽略的毒性。潜在的缺氧成像模式包括磁共振成像（MRI），它是非侵入性的，通过使用强磁场和射频脉冲，可以实现形态和功能解剖的可视化，基本上具有无限的深度穿透。利用MRI将利用这样一个事实，即铕的一种氧化态产生正的MRI对比，而氧化态则不会。另一种潜在的缺氧成像方式是光学成像，它也是一种非侵入性成像，是一种基于吸收和发射光的分子来可视化亚细胞形态的强大工具。那些既吸收光又发射光的材料被称为发光材料，对成像特别有用，因为人体中表现出发光的化学物质比那些只吸收光的化学物质少，从而产生更清晰的图像。用这种含铕试剂进行光学成像也可能产生良好的对比，因为铕的一种氧化态比另一种氧化态显示出更长的发光寿命。该项目将首先合成各种含铕显像剂，并对其化学和物理性质及稳定性进行表征，然后对这些显像剂进行体外MRI和缺氧光学成像测试，最后对这些成像方式进行体内测试。该项目属于EPSRC物理科学和医疗保健技术研究领域。