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Title: Quantitative Modelling of Positron Emission Tomography Tracer Pharmacokinetics in Hypoxia
Author: Kelly, Catherine
ISNI:       0000 0001 3596 609X
Awarding Body: Oxford University
Current Institution: University of Oxford
Date of Award: 2007
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Tumour hypoxia is a hallmark of solid tumours and is associated with a poor prognosis and response to therapy. The molecular imaging modality Positron Emission Tomography (PET), in conjunction with radiolabelled molecules called tracers, is a promising technique for the non-invasive quantitation of tumour hypoxia. In this thesis we use mathematical modelling techniques to characterise the relationship between tumour hypoxia and PET tracer distribution. In the first section, we investigate the impact of tumour vasculature on spatial profiles of tissue oxygen. The geometry of vasculature is a key determinant of the degree of hypoxia. Both the modal intervessel distance and the degree of variation in geometry exert significant effects on oxygen profiles. \Ve extend previous models by representing the vasculature as a piecewise-smooth function. This enables the coarse-scale simulation of tissue oxygenation, with little loss of accuracy compared to higher resolution simulations. In the second section, we characterise the relationship between tumour vasculature, hypoxia and the spatiotemporal distribution of the hypoxic tracer, 3-[18F]fluoro-l-(2-nitrol- imidazolyl)-2-propanol (Fmiso). The spatiotemporal distribution of Fmiso is highly dependent on the proximity of tissue to the vasculature, in agreement with previous studies. This model enables us to analyse the assumptions of a simple model that is frequently used to extract hypoxic information from Fmiso-PET studies. We find that the simplified model relates well to our more complicated 'ground truth' in characterising the degree of hypoxia, but is less suited to describing tracer transport. In the final section, we investigate the potential of another tracer, [18F]-2-Deoxy-2fluoro- O-glucose (FOG), as a marker of hypoxia. The relationship between hypoxia and FOG distribution is more complicated than that of Fmiso, so it is necessary to model hypoxia-dependent and -independent factors. \Ve find that the colocalisation of Fmiso and FOG at the sub-millimetre level is unlikely, as a result of their mechanistic differences. The model predicts that the influence of hypoxia-independent regulation of FOG uptake precludes the use of FOG as a marker of hypoxia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Oxford University, 2007 Qualification Level: Doctoral
EThOS ID:  DOI: Not available