Commonly noticed in the case of antiangiogenic agents and this phenomenon attributed to neovascular normalization. The longitudinal changes in median tumor pO2 values in groups of control and rapamycin treated mice are graphically displayed in Figure 4A. It can be seen that while the median pO2 values were similar in the two groups on day 0, rapamycin treated mice show higher tumor pO2 values on days 2 and 4. The median pO2 in the rapamycin treated group showed a small decrease on day 6, but it was at the same level as that on day 0. Similarly, the hypoxic fraction showed that rapamycin treated mice exhibit hypoxia to a lesser extent compared to control, untreated mice. Figure 4C shows the fractional blood volume in the tumors as a BMS-3 function of time. A significant decrease in blood volume in rapamycin treated mice compared to untreated mice was noticed on day 2. Continuing rapamycin treatment caused a further drop of blood volume on day 4 and day 6. An empirical analysis of tumor oxygenation status obtained from EPR imaging and the blood volume from MRI was done by obtaining the ratio of tumor pO2 with the fractional blood volume and plotted as a function of time and the results are shown in Figure 4D. The results show that oxygen delivery per fractional tumor blood volume in rapamycin treated mice was significantly more efficient than in control group of mice. In order to investigate the underlying mechanism associated with the observed improved tumor oxygenation, we carried out DCE-MRI study with 152918-18-8 Gd-DTPA as a contrast agent. It is well known that Gd-DTPA uptake is influenced by both tumor perfusion and vascular permeability. By considering only the initial rate of the Gd uptake the effects of changes in permeability on uptake can be minimized. Area under the curve of Gd-DTPA concentration in the SCC tumor calculated from the DCE-MRI results of initial 1 min after injection was 40% larger in 2 days rapamycin treated group compared to non-treated control group, indicating the improvement of blood flow in the SCC tumor by rapamycin treatments. Independent microscopic evaluation of tumor vasculature in control and rapamycin treated mice was carried out from tumor sections stained with CD31 for microvasculature and aSMA for pericyte coverage. A significant decrea
