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Title: Imaging angiogenesis in brain metastasis
Author: Buck, Jessica
ISNI:       0000 0004 7966 3498
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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Brain metastasis is responsible for a large proportion of the mortality of cancer, and there are currently no effective treatments. The effect of treatments, particularly anti-angiogenic therapeutics, is difficult to ascertain using current imaging methods. Thus, the aim of this thesis is to develop methods for imaging angiogenesis using magnetic resonance imaging (MRI) in a mouse model of brain metastasis. Arterial spin labelling (ASL) is an MRI technique that measures cerebral blood flow (CBF) non-invasively and quantitatively. The work described in this thesis optimised and validated multiphase pseudo-continuous ASL (MP pCASL) for use in mice. This sequence was then used to measure and identify areas of reduced CBF in mouse models of brain metastasis and glioma. Integrin αvβ3 is a marker of angiogenesis expressed on tumour blood vessels, including in brain metastasis. The second major aim of the work described in this thesis was to image angiogenic blood vessels in brain metastasis in vivo using microparticles of iron oxide (MPIO) conjugated to an integrin αvβ3 targeting peptide (RGD-MPIO). The targeted MPIO showed some specific binding in vivo, but were unsuccessful at visualising angiogenesis in vivo owing to pre-existing hypointense voxels in the tumour, and non-specific uptake of the MPIO. It was found that pre-existing hypointense voxels were caused by endogenous iron-laden macrophages resident in the tumour, and that non-specific contrast was a result of macrophage uptake of MPIO. It was also shown that non-specific macrophage uptake was reduced with antibody-targeted MPIO compared to peptide-targeted MPIO. In conclusion, whilst the use of MP pCASL was successful for imaging angiogenesis in brain metastasis, the use of RGD-MPIO was precluded owing, in large part, to non-specific uptake of peptide targeted MPIO.
Supervisor: Sibson, Nicola Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Oncology