Macromolecular contrast agents for Magnetic Resonance Imaging

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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.