This proposal is for a new small animal PET to support basic and translational research at the University of Washington and the Fred Hutchinson Cancer Research Center. This is an exciting time for imaging in biomedicine, with new imaging tools being developed to answer important questions at the cutting edge in all fields of biomedical research. Much of this research is conducted in small animal models of disease or special genetic expression. The value of these unique and highly specialized animal models has created a demand for biologically specific non-invasive imaging that can be performed longitudinally over the lifetime of the animal or expression of the disease. The UW Molecular Imaging Center is a focus for collaborative and innovative research using advanced methods for non-invasive imaging of biochemical processes in vivo. Our basic and translational research programs will benefit greatly from the high spatial and temporal resolution that a state of the art small animal PET can provide. The UW PET program has been active for nearly 20 years and is a leader in cancer and cardiovascular imaging research. One of the great successes of this program is that it has established collaborations with numerous departments spanning the UW, FHCRC and Children's Hospital and Region Medical Center. The success of this program has dictated a critical need to place a small animal PET in our institutions to support the research and imaging requirements of our NIH funded investigators and to support expanding other research programs. This application describes the use of small animal PET in many different research programs at our institutions, with a focus on cancer research applications. Projects that will initially be supported by this resource include mechanistic studies of hypoxia, tumor cell death, tumor metastasis, and tumor glucose metabolism; tumor response to therapy and therapy optimization; prostate cancer research; and optimization of [F-18]FDG scanning protocols. The proposed instrument will provide high resolution small animal PET imaging in conjunction with our radioisotope dedicated cyclotron, and group of researchers and staff with expertise in imaging, radiochemistry, physics, image analysis, kinetic modeling, molecular biology and study protocol development. The instrument we will acquire will be able to meet the high resolution imaging demands with count rate and attenuation correction capabilities to provide tissue quantitation of biologically specific radiopharmaceuticals required in small animal disease models. Imaging using PET radionuclides has become a remarkably useful translational tool for UW/FHCRC researchers, and has expanded considerably in the last several years. We now wish to complete our research capability with PET for researchers that also combine laboratory, small animal and human protocols. Acquisition and use of a dedicated state of the art small animal PET will make a significant contribution to the translational research goals of our highly motivated and distinguished group of investigators. ? ? ?