Molecular Imaging in Cancer
Previous and current research
Magnetic resonance imaging (MRI) is a well-established, clinically applicable, tool for determining tissue morphology. The techniques of molecular imaging seek, through the use of appropriate probe molecules, to transfer into the MR image of tissue anatomy, information about underlying tissue biochemistry and physiology. We are developing novel magnetic resonance-based molecular imaging techniques to detect the early responses of tumours to therapy, with a view to translating these into clinical application. This has included methods for detecting and predicting responses to an anti-vascular drug and for detecting early tumour responses to immunotherapy. An early apoptotic response following treatment with a chemotherapeutic drug is a good prognostic indicator for treatment outcome. Therefore, a major focus is the development of magnetic resonance imaging (MRI) and spectroscopy (MRS) methods for the non-invasive detection of tumour cell apoptosis in vivo.
Through a commercial partnership, we are developing nuclear spin hyperpolarisation as a novel tool for molecular imaging. Nuclear spin polarisation offers enormous gains in sensitivity, as much as 10,000x, which makes it possible not only to image the distribution of isotopically-labelled cellular metabolites, but also their enzymatic transformation into other species. This approach could revolutionise molecular imaging using MR techniques, giving new insights into disease processes in vivo.
Another interest is in the field of metabolomics. We have shown that 1H MRS-based metabolite profiling can be used to classify yeast mutants and have proposed this as a method for functional analysis of the yeast and other genomes. Recent results suggest that this approach can also give new insights into the structure of a metabolic network. In the field of cancer, we have shown that we can distinguish transcription factor gene knockouts (p53 and p300) in tumour cell lines on the basis of the resulting MRS-defined metabolite profiles. In addition to providing new insights into the biology of these transcription factors, this approach may also be useful in the analysis of patient tumour biopsies, where the expectation is that it could be used to give information about drug sensitivity and prognostic information about treatment outcomes.
Future projects
- Development of novel gene reporter constructs for use with MRI.
- Hyperpolarised imaging methods for detecting tumour cell proliferation and apoptosis.
- Further development of a targeted MRI contrast agent for detecting tumour cell apoptosis.
- Metabolomic methods for network analysis and for predicting tumour responses to therapy.
