Effect Of Carbogen On Tumor Oxygenation Status By Probe Po2 Measurement And Hypoxia Imaging Study

Tumor hypoxia, a common phenomenon in solid neoplasms has been associated with aggressive malignant phenotypes and resistance to chemo- and radiotherapy. The purpose of the study was to investigate the effect of carbogen on oxygenation status in tumoral and muscular tissues by direct probe pO2 measurement, to compare the difference of hypoxia biodistribution by imaging exogenous and endogenous hypoxia markers and to explore potential hypoxia-modifying modality to enhance the effect of radiotherapy. BALB/c-nu/nu nude mice were used as tumor-bearing host. pO2 measurements in tumoral and muscular tissues were initiated at the time of probe insertion and the values were recorded continuously for at least 60 min using the fiber-optic oxygen-sensing device (OxyLiteÔ Oxford Optronix, UK) when the tumor-bearing host was under anesthesia which was accomplished with a gas mixture containing 1.0% isoflurane balanced by either air (21% O2) or carbogen (95% O2 + 5% CO2). Image study with CA IX and exogenous hypoxia markers including pimonidazole and EF5 was used to evaluate the effect of spatial biodistribution when animals were treated with air- and carbogen-breathing. Hypoxia in tumor is heterogeneously observed in solid tumors when animal breathing air by using probe pO2 measurement or image study, whereas it ameliorated when breathing carbogen. 4 patterns of pO2 response in tumor can be subcategorized as: i) immediate response, ii) moderate immediate response, iii) slow response and iv) no response when animal was switched from air to carbogen breathing; while 2 patterns, i.e., immediate or no response in muscular tissue are observed. pO2 values in tumoral tissue may remain at relatively higher level at 30 or 60 minutes when the breathing gas was switched from carbogen to air than that of the baseline at initial air breathing; while pO2 value in muscular tissue at air breathing switched from carbogen returned to the same level of baseline at initial air breathing. Tumor hypoxia existed heterogeneously within tumor tissues thus could be subcategorized into 4 patterns according to the pO2 response to carbogen breathing. The observation that pO2 value may remain at relatively high level when air breathing was switched from carbogen in comparison to the baseline at initial air breathing may provide a potential modality that radiation therapy may benefit immediately after carbogen-breathing by improved oxygen status in tumor but not in muscular tissue thus may enhance the therapeutic index. Further research should be merited.