The central hypothesis of the current P01 Application is that the development of non-invasive imaging of tumor hypoxia will lead to improved management of solid-tumor patients and advance our understanding of the molecular and biological mechanisms underlying tumor hypoxia images. A multi-modality approach, integrating and comparing positron emission tomography (PET) and nuclear magnetic resonance (NMR) imaging, is proposed. For PET imaging, two promising radiotracers that specifically target hypoxic cells (124I-IAZG and 18F-FMISO) and relevant trans-genes and (124I-FIAU and 18F-FEAU) will be synthesized with our cyclotron and investigated, and for NMR, different parametric indices (e.g. perfusion, lactate levels) will be evaluated as surrogate markers of tumor hypoxia. The function of Core C, the Imaging and Radiochemistry Core, is to therefore provide state-of-the-art in vivo and ex vivo imaging capabilities and positron-emitting radiotracers - both for small animals (rodents) in laboratory investigations and for human subjects in clinical investigations - for the Research Projects and the other Cores. Inaddition to the availability of new PET-CT scanners for clinical studies, our Core provides an array of state-of-the art small-animal imaging and support systems - microPET, MS bioluminescence and fluorescence optical imaging, X-SPECT microSPECT-microCT, microCAT II microCT, 4.7-T 40-cm bore and 7.0-T 31-cm Bruker NMR systems, high-resolution phosphor-plate digital autoradiograph, and digital microscopy. A key component of our Program Project and, in particular, this Core is our ongoing development of a practical, generally applicable method - including all necessary hardware and software - for truly multi-modality as well as intra-modality image registration in animal studies. The image registration method we are developing provides the capability of precise image registration over a broad 'dynamic range' - from ultra-high-resolution digital autoradiograms (< 100 (mu m) and histological-section images (< 10 mu m) to coarser-resolution (approximately 100 mu m (NMR, microCT) to approximately 1,000mu m (microPET, microSPECT)) in vivo images. Corroboration by direct comparison of unambiguously registered images acrossthese multiple modalities will not only expedite validation of new tracers and new imaging and image-analysis methods but mayalso provide unique, therapeutically important insights into the underlying biology of tumors (such as the effect of interactingfactors such as glucose metabolism, blood flow, hypoxia, lactate levels, etc.) on tumor response to therapy.
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