Macromolecular contrast agents for Magnetic Resonance Imaging

磁共振成像（MRI）是一种非常宝贵的工具，用于成像肿瘤和诊断疾病。尽管MRI在临床上得到了广泛应用，但该技术最大的缺点是灵敏度不够。出于这个原因，已经开发了造影剂来降低周围水分子的弛豫时间，增加“弛豫率”并使图像变亮。基于钆的造影剂经常使用，其由被强螯合配体包围的钆（III）离子组成。然而，商业造影剂远非最佳，弛豫率远未接近理论最大值。我们已经设计了大环Gd（III）配合物轴承两个可聚合的武器，它可以很容易地聚合在一个单一的步骤，形成不同的架构的共聚物。通过交联降低Gd（III）络合物的局部旋转运动，我们开发了与商业造影剂相比具有显著增加的弛豫率的大分子造影剂。大分子具有增加的动力学稳定性，减少脱甲氨蝶呤的机会，和更高的效率，潜在地降低所需的剂量浓度。本项目旨在通过将该系统与用于双重成像技术的发光探针相结合，进一步开发大分子造影剂，将单体复合物掺入刺激响应颗粒中以诱导对不同组织中生理参数（如pH）变化的响应，并扩大聚合范围。

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.