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17 March 2015 MRI assessment of changes in tumor oxygenation post hypoxia-targeted therapy
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Abstract
In the tumor microenvironment, the combination of compromised oxygen supply and high demand results in formation of regions of acute and chronic hypoxia, which promotes metastasis, proliferation, resistance to chemo and radiotherapy and poor prognosis. Targeted, non-invasive in vivo imaging of hypoxia has the potential to determine regions with poor oxygenation in the target and differentiate between normoxic vs hypoxic tissues. MRI provides a powerful platform for generating quantitative maps of hypoxia with the use of a novel pO2 measuring technique PISTOL (Proton imaging of siloxanes to map tissue oxygenation levels) which could impact the therapeutic choices. In the present study, PISTOL was used to determine the changes in oxygenation of tumor in pre-clinical models of NSCLC (H1975) and epidermoid carcinoma (A431) in response to tirapzamine (TPZ), a hypoxia activated chemotherapeutic. The tumor volume measurements indicate that tirapazamine was more effective in slowing the tumor growth in H1975 as compared to A431 tumors, even though lower baseline pO2 was observed in A431 as compared to H1975 tumors. These results indicate that other factors such as tumor perfusion (essential for delivering TPZ) and relative expression of nitroreductases (essential for activating TPZ) may play an important role in conjunction with pO2.
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Shubhangi Agarwal, Rohini Vidya Shankar, Landon J. Inge, and Vikram Kodibagkar "MRI assessment of changes in tumor oxygenation post hypoxia-targeted therapy", Proc. SPIE 9417, Medical Imaging 2015: Biomedical Applications in Molecular, Structural, and Functional Imaging, 941714 (17 March 2015); https://doi.org/10.1117/12.2083926
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