Responsive Lanthanide Probes
We successfully developed an enzyme-activated Gd-based MR contrast agent that, in vitro, showed an ~90% increase in relaxivity on activation by esterase. This showed great promise for cellular imaging via an amplification and accumulation strategy. Luminescence studies on corresponding Eu(III) complexes helped to confirm these results. We also developed pH-responsive luminescence/MR lanthanide probes. Relaxivity (Gd) and luminescent emission intensity (Eu) are modulated by pH changes. Of particular interest is the ratiometric pH response of Eu(III) complexes enabling concentration independent pH determination.
Design and Synthesis of Novel Lanthanide Chelates for use in Magnetic Resonance Imaging (MRI)
Propargyl-appended Ln(III) complexes were shown to have unanticipated reactivity towards NaN3 in the Cu(I) catalysed ‘click’ reaction yielding unsubstituted 1,2,3-triazoles. The implications with respect to MRI contrast agents were investigated. Strategies for functionalising MRI contrast agents using Click Chemistry are being explored. New contrast agents for magnetic resonance angiography have also being developed. Hydrophobic binding moieties are linked to Gd(III) chelates. On binding to Human Serum Albumin an increase in MR signal intensity is observed. Photophysical properties of corresponding Eu(III) complexes, enabling binding constants to be determined from luminescence studies; these complement those obtained from relaxation rate enhancements of Gd(III).
Dual Mode Imaging Agents
Molecular Imaging (MI) and Magnetic Resonance (MR) contrast agents are at the forefront of medical research and drug discovery. Current research in MI focusses on e.g. simultaneous microscopy and whole body imaging, so-called “multimodal” imaging. MR enables high spatial resolution and the ability to simultaneously obtain physiological and anatomical information, whereas optical (fluorescence) imaging allows for rapid screening. Combining the advantages of both imaging modalities allows: e.g. co-validation of the accumulation of targeted MR contrast agents at a target site. We are combining components of both imaging modalities in the same compound.
Theranostic Metal Complexes
This project aims to develop theranostic compounds based on a core coordination compound. These complexes are designed to deliver and release therapeutic drugs whilst simultaneously acting as diagnostic imaging agents.