Collingridge, David R.; (1997) Measurement and manipulation of tumour oxygen tension. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis investigates a range of techniques designed to measured tumour oxygenation in vivo, and their ability to monitor modalities which improve oxygen tension. In addition, the relationships between pO2 measurements, radiobiological hypoxia, and treatment response are also examined. Oxygen tension measurements are performed in 24 experimental tumour models with the Eppendorf pO2 histograph. These measurements show that tumour tissue is poorly oxygenated relative to normal tissue. Real-time pO2 measurements using a prototype luminescence-based optical sensor and a pulsed polarographic electrode, demonstrate that tumour oxygenation can fluctuate temporally and have microregional heterogeneity. The luminescence sensor and the pO2 histograph yield comparable oxygen distributions for the SaF murine tumour, although, the optical sensor readings are significantly higher in the low range (<2.5 mmHg) reflecting less oxygen depletion. The pulsed polarographic electrode is unable to measure microregional heterogeneity due to a large sampling volume, and can be susceptible to oxygen contamination from external sources. Under optimal conditions, all three sensors have near identical accuracy, and measure similar oxygen tensions in the SaF tumour. pO2 measurements in the SaF and FSaN tumours do not match the radiobiologically hypoxic fractions nor the proportion of tumour cells labelled with a bioreductive marker. However, carbogen breathing with or without co-administration of nicotinamide or pentoxifylline is shown to improve tumour oxygenation in a time-dependent manner, and carbogen alone radiosensitises the SaF tumour. In clinical studies, human tumour pO2 is comparable with experimental tumours, and relative improvements in tumour pO2 with carbogen breathing and 2% CO2/ 98% O2 are similar to those seen with the SaF tumour. BOLD imaging and 19F MRI are shown to have clinical potential to monitor tumour oxygenation and blood flow, whilst 31P spectroscopy does not detect any effect on the microenvironment of the SaF and CaNT during carbogen breathing.

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