Effects of nicotinamide and carbogen on oxygenation in human tumor xenografts measured with luminescense based fiber-optic probes.
OBJECTIVE
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 helpful for selecting patients for these new treatment approaches.


METHODS
The fiber-optic oxygen-sensing device, OxyLite, was used to measure changes in pO(2), 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 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 the 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 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.


CONCLUSIONS
Temporal changes in local pO(2) can be measured with the OxyLite. This system was used to quantitate the effects of oxygen modifying treatments. Rapid increases in pO(2) 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 pO(2) determination gives spatial information about the distribution patterns of tumor hypoxia at the microscopic level together with the possibility to continuously measure changes in pO(2) in specific tumor areas.
Bussink
J
J
Department of Radiation Oncology, Joint Centre for Radiation Oncology Arnhem-Nijmegen, UMC St. Radboud, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Kaanders
J H
JH
Strik
A M
AM
van der Kogel
A J
AJ
D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D005336:Fiber Optic Technology; D006801:Humans; D016014:Linear Models; D008163:Luminescent Measurements; D009536:Niacinamide / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D055100:Optical Fibers; D010100:Oxygen / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C033815:pimonidazole; C011700:carbogen; D010100:Oxygen