Molecular imaging techniques have revolutionised our understanding of disease
states and the underlying processes causing their occurrence. Such a feat would not
have been accomplished without the utilisation of the imaging probes central to the
field of molecular imaging. The work undertaken in this thesis describes the synthesis
and biological evaluation of lipidic contrast agent probes, designed for effective
cellular entry and solid tumour imaging.
A gadolinium (Gd) based paramagnetic lipid (Gd.DOTA.DSA) was synthesised and
liposome formulations containing this lipid were optimised for maximum cellular
labelling. MRI signal enhancing properties of bimodal paramagnetic-fluorescent
liposomes utilising Gd.DOTA.DSA was shown both in vitro and in vivo. Tumour MRI
results revealed these liposomes to benefit from a prolonged in vivo circulation time
and excellent tumour accumulation properties as co-validated by both MRI and
fluorescence microscopy of tumour sections. Here, the enhanced permeation and
retention (EPR) effect of tumour tissue was exploited, whereby nanoparticles such as
the paramagnetic liposomes described, are able to accumulate in tumour tissue due
to leaky endothelial layers of damaged blood vessels.
A further bimodal fluorescent and paramagnetic lipid (Gd.DOTA.Rhoda.DSA) was
designed and synthesised and was shown to label cancer cells in vitro and effectively
enhance tumour MRI signal in vivo. These results were also analysed by MRI and
fluorescence modalities.
Work towards a trimodal fluorescent, 1H and 19F MRI agent was undertaken and
prospective routes for its final synthesis purposed.