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Title: Design, synthesis and evaluation of multimodal paramagnetic lipids for liposomal fluorescence and magnetic resonance imaging
Author: Kamaly, Nazila
ISNI:       0000 0001 3594 2530
Awarding Body: Imperial College London (University of London)
Current Institution: Imperial College London
Date of Award: 2008
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Molecular imaging is a large field encompassing a range of techniques which allow for visualisation of disease processes at the molecular and cellular level. These techniques range from radionuclide, fluorescence and bioluminescence based to magnetic resonance based. Magnetic resonance imaging (MRI) is a clinical imaging technique that benefits from a high degree of spatial resolution and is capable of producing opaque 3D images of tissues within the millimetre range consistently and in a short period of time. The project described is based on the development of contrast agents which are capable of further enhancing images obtained with MRI. The synthesised agents are lipidic based and can therefore be used to formulate liposomes, which are then subsequently used to label cells for cd tracking studies, or used to image tumours in vivo. A further potential of these paramagnetic liposomes is their ability to deliver therapeutic agents such as drugs or nucleic acids into cells and as such their in vitro transfection efficiency was also assessed. Bimodal and trimodal liposomal components were also synthesised and developed to allow for a multimodal imaging platform whereby liposomal particles can be tracked by fluorescel1ce, 1H and 19 F magnetic resonance imaging. Using a combination of solution and solid phase chemistry, paramagnetic and fluorescent lipids were synthesised and characterised. The optimal liposome formulation for in vitro cell labelling was determined along with cytotoxicity studies. MR images of labelled cells were obtained and liposomal uptake into cells determined and validated with fluorescence microscopy. Paramagnetic liposomes were injected into tumour bearing mice and a substantial increase in tumour signal post injection was observed. The paramagnetic liposomes were further functionalised by incorporating a targeting moiety selective for human ovarian cancer cells. A drastic improvement in signal enhancement ability was observed by MRI for targeted liposomes compared to non-targeted liposomes.
Supervisor: Miller, Andrew ; Bell, Jimmy Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral