Alonzi, R.; (2008) Evaluation of the oxygenation and vascularity of prostate cancer using magnetic resonance imaging. Doctoral thesis , University of London.

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Abstract

The outcome of radical treatment for prostate cancer is appreciably influenced by the presence of hypoxia. Oxygenation status may therefore be another underlying biological parameter, beyond the classic prognostic factors (age, clinical stage, Gleason score and prostate specific antigen), that predicts for treatment failure in this malignancy. Angiogenesis plays a pivotal role in the growth, invasion, metastasis and survival of prostate tumours. Measurements of angiogenesis have been linked with clinical and pathological stage, histological grade and the potential for metastasis formation. They also provide prognostic information and have been correlated with disease-specific survival and progression after treatment. Magnetic resonance imaging techniques are capable of detecting the molecular, biochemical, physiological and metabolic changes that occur due to pathological processes within tissues. Experiments presented in this thesis have sought to evaluate the ability of Dynamic Contrast Enhanced MRI (DCE-MRI), Dynamic Susceptibility Contrast MRI (DSC-MRI), Intrinsic Susceptibility Weighted MRI (also known as Blood Oxygen Level Dependent (BOLD) MRI) and Diffusion Weighted Imaging (DWI) to characterise the oxygenation and vascular status of prostate tumours in animal models and in patients with prostate cancer. This research has demonstrated the feasibility of hypoxia imaging in prostate cancer. Although MRI can not precisely map tissue p02, the combination of BOLD-MRI and dynamic susceptibility contrast MRI provides a valuable surrogate and predicts the pattern of hypoxia, as determined by pimonidazole immunohistochemistry, with reasonable accuracy. The research has also shown that prostate cancer responds to carbogen gas breathing and that androgen deprivation causes profound vascular collapse within one month of starting therapy. These findings should help in the rational design of future studies that aim to target tumour vasculature and combat tumour hypoxia in prostate cancer.

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