A) T1-weighted pO2 imaging using Saturation by fast recovery (SFR): Oxygen-induced line broadening of injected paramagnetic tracers forms the basis of EPR imaging of tissue pO2 using a T2* based approach. However in cases of the paramagnetic tracer Oxo63 or Oxo 71 accumulating locally at concentrations 5 mM the contribution of self-broadening to the overall line width may cause an overestimation of pO2. To avoid this, a T1 based approach has been evaluated using a saturation by fast recovery strategy. This method avoids concentration induced line broadening. We have made a comparative assessment of the EPR SFR approach with T2* based pO2 and T2/Echo-based pO2 assessment. Our studies showed a distinct benefit of pO2 imaging in terms of improved precision in the range of 0 - 20 mm Hg which is relevant for in vivo studies. B) EPR Imaging of tumor pO2 to guide therapy: Hypoxia is a known cause of resistance to radiotherapy. To overcome this, hypoxia activated prodrugs are developed. Not all tumors have hypoxia and also tumors which have hypoxic regions have aerobic fractions as well. A priori knowledge of the presence and the extent of hypoxia is useful in developing appropriate treatment strategies. We have used EPR imaging to characterize tumors based on their tumor O2 in three pancreatic tumor xenografts namely: Hss766t, MiaPAca-2, and Su86.86. Based on tumor pO2 status, we find the tumor pO2 to follow Su86.86MiaPaca-2Hs766t. Based on this information we examined if this can be used as predictor of therapy response to ionizing radiation or a hypoxia-activated prodrug TH-302. Groups of tumor bearing mice were treated to 5 fractions of 3 Gy each or to TH-302. We find the tumor growth delay studies to show that while ionizing radiation to be effective in the order of Su86.86MIaPAca-2Hs766t. Similarly The response to TH-302 was found to follow the order of HS766tMiaPaca-2Su86.86. These studies suggest that EPR imaging can be useful to devise appropriate treatments.
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