Purpose-Tumor hypoxia has long been known to produce resistance to radiation. In this study, electron paramagnetic resonance (EPR) oxygen imaging was investigated for its power to predict the success of tumor control depending on tumor oxygenation level and radiation therapy dose.Methods and Materials-Thirty-four EPR oxygen images were obtained from the legs of C3H mice bearing 0.5 ml FSa fibrosarcomas under both normal (air breathing) and clamped tumor conditions. Under the same conditions as those during which the images were obtained, tumors were irradiated to a variety doses near the FSa TCD 50 . Tumor tissue was distinguished from normal tissue using co-registration of the EPR oxygen images with spin-echo MRI images of the tumor and/or stereotactic localization. Tumor voxel statistics in the EPR oxygen image included mean and median pO 2 , and the fraction of tumor voxels below the specified pO 2 values of 3, 6 and 10 torr. Bivariate logistic regression analysis using radiation dose and each of the EPR oxygen image statistics determined which best separated treatment failure from success.Results and Conclusions-TCD 50 measurements were similar to those found in the literature for this syngeneic tumor. Bivariate analysis of 34 tumors demonstrated that tumor cure correlated with dose (p=0.004) and with <10 torr hypoxic fraction (p=0.023). Together, radiation dose and EPR image hypoxic fraction separate the population of FSa fibrosarcomas which are cured from those which fail, thus predicting curability.

No abstract

No abstract

No abstract

Structural breakdown of the cell membrane is a primary mediator in trauma induced tissue necrosis. When membrane disruption exceeds intrinsic membrane sealing processes, biocompatible multi-block amphiphilic copolymer surfactants such as Poloxamer 188 (P188) have been found to be effective in catalyze or augment sealing. Although in living cells copolymer induced sealing of membrane defects has been detected by changes in membrane transport properties, it has not been directly imaged. In this project we used Atomic force microscopy (AFM) to directly image saponin permeabilized and poloxamer sealed plasma membranes of monolayer cultured MDCK and 3T3 fibroblasts. AFM image analysis resulted in the density and diameter ranges for membrane indentations per 5×5 μm area. For control, saponin lysed, and P188 treatment of saponin lysed membranes, the supra-threshold indentation density was 3.6 ± 2.8, 13.8 ± 6.7, and 4.9 ± 3.3/cell, respectively. These results indicated that P188 catalyzed reduction in size of AFM indentations which correlated with increase cell survival. This evidence confirm that biocompatible surfactant P188 augment natural cell membrane sealing capability when intrinsic processes are incapable alone.