Macromolecular contrast agents for Magnetic Resonance Imaging

磁共振成像用高分子造影剂

• 批准号: 2306284
• 金额: --
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2306284
• 关键词: Macromolecular; contrast; agents; Magnetic; Resonance

Magnetic resonance imaging (MRI) is an invaluable tool for imaging tumours and diagnosing disease. Despite the widespread use of MRI in the clinic, the largest downfall of the technique is itslack of sensitivity. For this reason, contrast agents have been developed to lower the relaxation time of surrounding water molecules, increasing 'relaxivity' and brightening the image. Gadolinium based contrast agents are regularly used, consisting of a gadolinium(III) ion surrounded by a strongly chelating ligand. However, commercial contrast agents are far from optimal, and the relaxivity is nowhere near the theoretical maximum value. We have designed macrocyclic Gd(III) complexes bearing two polymerisable arms, which can be readily polymerised in a single step to form copolymers with different architectures. By decreasing the local rotational motion of the Gd(III) complex through crosslinking, we have developed macromolecular contrast agents with significantly increased relaxivity compared withcommercial agents. The macromolecules have increased kinetic stability, reducing the chances of demetallation, and higher efficiency, potentially decreasing the dose concentration required. This project aims to further develop macromolecular contrast agents by combining the systems with luminescent probes for dual imaging techniques, incorporating the monomeric complexes into stimuli responsive particles to induce response to changes in physiological parameters such as pH in different tissues and expanding the scope of the polymerisations.

磁共振成像（MRI）是肿瘤成像和疾病诊断的宝贵工具。尽管MRI在临床上被广泛使用，但该技术最大的缺点是灵敏度不够。由于这个原因，造影剂已经被开发出来，以降低周围水分子的松弛时间，增加“松弛度”，使图像更亮。以钆为基础的造影剂通常被使用，由一个被强螯合配体包围的钆（III）离子组成。然而，商用造影剂远未达到最佳效果，松弛度也远未达到理论最大值。我们设计了具有两个可聚合臂的大环Gd（III）配合物，可以很容易地在一个步骤中聚合形成具有不同结构的共聚物。通过交联降低Gd（III）配合物的局部旋转运动，我们开发出了与商用造影剂相比具有显著增加弛豫度的大分子造影剂。大分子增加了动力学稳定性，减少了脱金属的机会，效率更高，潜在地降低了所需的剂量浓度。该项目旨在进一步开发大分子造影剂，将该系统与用于双重成像技术的发光探针相结合，将单体复合物结合到刺激响应粒子中，以诱导对不同组织中pH等生理参数变化的响应，并扩大聚合的范围。