Effects of nicotinamide and carbogen on oxygenation in human tumor xenografts measured with luminescense based fiber-optic probes

Background and purpose: In head and neck cancer, addition of both carbogen breathing and nicotinamide to accelerated fractionated radiotherapy showed increased loco-regional control rates. An assay based on the measurement of changes in tumor pO₂ in response to oxygenation modification could be helpful for selecting patients for these new treatment approaches. Materials and methods: The fiber-optic oxygen-sensing device, OxyLite™, was used to measure changes in pO₂, at a single position in tumors, after treatment with nicotinamide and carbogen in three human xenograft tumor lines with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image processing system. Results: At the position of pO₂ measurement, half of the tumors showed a local increase in pO₂ after nicotinamide administration. Steep increases in pO₂ were measured in most tumors during carbogen breathing although the increase was less pronounced in tumor areas with a low pre-treatment pO₂. A trend towards a faster local response to carbogen breathing for nicotinamide pre-treated tumors was found in all three lines. There were significant differences in hypoxic fractions, based on pimonidazole binding, between the three tumor lines. There was no correlation between hypoxic marker binding and the response to carbogen breathing. Conclusion: Temporal changes in local pO₂ can be measured with the OxyLite™. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO₂ during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was smaller and more variable. Bio-reductive hypoxic cell marker binding in combination with OxyLite™ pO₂ determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO₂ in specific tumor areas.