Quantification of Micro-Regional Heterogeneities in Tumor Oxygenation Using Intravascular HbO 2 Saturations

Abstract

Despite promising reports as to the relationship between tumor radiosensitivity and overall tumor oxygenation, little additional information has been forthcoming regarding the importance of localized variations in tumor oxygen distribution. The objectives of the current study were (1) to devise a strategy for sampling tumor HbO2 saturation distributions and (2) to compare intratumor heterogeneities in HbO2 profiles with intertumor variability to determine whether representative tumor oxygen profiles can be obtained from a limited tumor sample. Using murine KHT fibrosarcomas, maps of tumor intravascular HbO2 saturations were obtained using cryospectrophotometric techniques and without the use of anesthetics. Micro-regions composed primarily of either high or low HbO2 vessels were observed in both peripheral and interior regions of the KHT tumors, although HbO2 levels were higher, on average, toward the periphery. To quantify intra- and intertumor heterogeneities in oxygen delivery, alternative HbO2 sampling protocols were evaluated in comparison to all-inclusive HbO2 maps for each tumor cross section. Since intratumor variations in HbO2 distributions were of the same order of magnitude as intertumor variations for tumors of a single tumor line, it is clear that tumor micro-regional physiology cannot be characterized adequately by a single regional sample.