? The investigators applying for this grant have as their long-term objectives the development of new tools to benefit the fields of cancer, vascular biology, tissue engineering, and to answer fundamental biological questions. This instrument will provide an accurate, cost-effective method to measure the results of in vivo experiments. The use of this machine is predicted to substantially reduce the amount of animals required for the in vivo work associated with their respective grants. In addition, the sensitivity of this instrument will allow tracking of cells and small tumors at a level that is not currently possible. For example, most deaths from cancer are caused by metastatic growth, not by the primary tumor. More sensitive detection of small, previously undetectable metastases, will provide a greater understanding of the mechanisms of tumor metastases. Dormant tumors, which are microscopic in size will also be detected and followed to better understand the phenomenon of dormancy. The increased sensitivity will enable the tracking, for example, of catalytic activity and promoter activity that have previously been feasible only in in vitro assays. Because the animals will be monitored using this non-invasive technology they will not have to be sacrificed to track the progress of an experiment. The power of this new technology provides a tool that will expedite ongoing research and make possible new in vivo research designs that were not previously possible. As an example, this instrument will give us the ability to incorporate orthotopic tumor models to far greater advantage. These tumors will be able to be followed through their entire course without having to sacrifice animals at each time point. A further advantage is that large scale screening of mice will be possible in tumor models such as brain where invasive techniques cannot be performed without destroying the experiment. Current methods of following cells, such as transfection of green flourescent protein into candidate cells, do not have the sensitivity to be detected easily or accurately in vivo and are further limited by surface expression. This luciferase-based technology affords a superior method to achieve this aim. ? ?
