A revolution in the use of mouse models in oncology research has been created by combining sophisticated mouse models of human disease with bioluminescent reporter systems. Highly sensitive imaging systems optimized for quantifying the bioluminescent signals offer researchers the opportunity to monitor biological processes taking place in a living mammal in real time, with high sensitivity and high throughput. The information gained from this molecular imaging approach is generally unobtainable from other imaging modalities, and current commercial imaging systems are straightforward to use and inexpensive to maintain. A number of investigators at Fox Chase Cancer Center (FCCC) are currently engaged in, or are developing, animal models that will require access to a state-of-the-art bioluminescent imaging (BLI) system. Transgenic luminescent animals, or tumors derived from cell lines transfected with luminescent genes grown in immunocompromised host animals will be imaged to study molecular changes in animals in response to treatment, detect small metastatic tumors, and follow tumor growth in serial experiments. These experiments will use far fewer animals than traditional methods of serial sacrifice, and provide us with a real time assay of target gene expression for molecularly targeted therapies. BLI equipment will complement our existing small animal MRI scanner (currently the only imaging modality available at FCCC), and acquisition of this equipment is the logical next step in our long term plans to create a multi-modal animal imaging suite. Project Relevance: This proposal will present a broad range of preclinical research, including chemotherapy in colon cancer, the role of combination therapies for the treatment of primary and metastatic tumors in prostate cancer, the role of disruptions in protein synthesis, the role of hormone interactions in breast cancer, and the phenomenon of tumor resistance to therapy because of the poor vasculature exhibited by many tumor types. The information gained will guide researchers in the appropriate use of the therapeutic or preventive agents being studied, and elucidate the roles of specific molecular events in tumor formation and development. ? ? ?
