Macromolecular contrast agents for Magnetic Resonance Imaging

磁共振成像(MRI)是肿瘤成像和疾病诊断的宝贵工具。尽管核磁共振在临床上得到了广泛的应用，但这项技术最大的缺陷是缺乏敏感性。出于这个原因，造影剂已经被开发出来，以降低周围水分子的松弛时间，增加松弛程度，并使图像变亮。通常使用的造影剂是由一种被强烈螯合配体包围的Gd(III)离子组成。然而，商业造影剂并不是最理想的，弛豫度也远未达到理论上的最大值。我们设计了带有两个可聚合臂的大环Gd(III)配合物，这些配合物可以很容易地一步聚合成不同结构的共聚物。通过交联减少Gd(III)络合物的局部旋转运动，我们研制出了与商业试剂相比具有显著提高弛豫度的大分子造影剂。这些大分子增加了动力学稳定性，减少了脱金属的机会，并提高了效率，潜在地降低了所需的剂量浓度。该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来进一步开发大分子造影剂，将单体络合物掺入刺激响应粒子中，以诱导对不同组织中的生理参数(如pH)的变化的响应，并扩大聚合的范围。

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.