The fundamental hypothesis driving this program is that the development and clinical implementation of non-invasive imaging of tumor hypoxia will lead to improved management of patients with solid tumors. However, the hypoxic phenotype is complex and in order to assess the clinical value of noninvasive images of tumor hypoxia, we must first understand the mechanisms operating at a microscopic level that are responsible for the generation of the macroscopic images. For an imaging procedure to successfully discriminate between hypoxic and non-hypoxic tumors at the global level it must also, when examined with sufficient spatial resolution, reflect the differences in hypoxia that exist within tumors at a microscopic level. There is no single """"""""gold standard"""""""" technique for determining tumor hypoxia that can be used to verify all the others - each technique has its own particular strengths and weaknesses. This means we must use multiple techniques with the goal of achieving a consensus and require a systematic approach to registration, correlation and validation. The role of the tumor and radiation biology core is to provide a set of model systems and assays that enable tumor hypoxia to be studied and the components of the multi-modality imaging approach to be compared with relevant biological indices. The specific tasks of this core are to: 1. characterize tumor cell lines in terms of their oxygen-dependent behavior in-vitro and tumor morphology in-vivo and identify suitable model systems for study by the research projects; 2. generate and characterize appropriate tumor cell lines stably transfected with the TKeGFP fusion gene expressed either constitutively or under the control of a hypoxia response element; 3. implement and validate immunohistochemical methods of detecting endogenous markers related to tumor hypoxia and exogenous tracers of tumor hypoxia; 4. implement and validate assays of radiobiological damage in tumor samples and sections; 5. optimize the use of invasive oxygen probes to measure intratumoral oxygen tension.
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