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 pO(2) in response to oxygenation modification could be he lpful for selecting patients for these new treatment approaches. Materials and methods: The fiber-optic oxygen-sensing device, OxyLite(TM), was used to measure changes in pO(2), at a single position in tumors, after treatment with nicotinamide and carbogen in three human zenograft tumor li nes with different vascular architecture and hypoxic patterns. Pimonidazole was used as a marker of hypoxia and was analyzed with a digital image proc essing system. Results: At the position of pO(2) measurement, half of the tumors showed a local increase in pO(2) after nicotinamide administration. Steep increases in pO(2) were measured in most tumors during carbogen breathing although th e increase was less pronounced in tumor areas with a low pre-treatment pO(2 ). A trend towards a faster local response to carbogen breathing for nicoti namide pre-treated tumors was found in all three lines. There were signific ant differences in hypoxic fractions, based on pimonidazole binding, betwee n the three tumor lines. There was no correlation between hypoxic marker bi nding and the response to carbogen breathing. Conclusion: Temporal changes in local pO(2) can be measured with the OxyLit e(TM). This system was used to quantitate the effects of oxygen modifying t reatments. Rapid increases in pO(2) during carbogen breathing were observed in most tumor areas. The locally measured response to nicotinamide was sma ller and more variable. Bio-reductive hypoxic cell marker binding in combin ation with OxyLite(TM) pO(2) determination gives spatial information about the distribution of patterns of tumor hypoxia at the microscopic level toge ther with the possibility to continuously measure changes in pO(2) in speci fic tumor areas. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved .