Observing the expression of transfected genes in a living system, with minimal disturbance, is important for the future development of gene therapy. We propose an approach that possesses many of the best features of recent advances in this area, but extends the power of imaging in new directions. The metallic elements possess a variety of useful physical properties that make them valuable as probes. These include radioactive emissions of photons for gamma or PET imaging, radioactive emissions of particles for therapy, paramagnetism for MRI contrast, luminescence for optical imaging, etc. Chemistry for making use of these properties in biomedical applications is fundamental to the further development of imaging instrumentation and technology. We will demonstrate the feasibility of imaging gene expression with metal chelates by engineering an antibody so that it is expressed as a cell-surface receptor for metal chelates, under the control of an inducible transcription unit. When expressed on the cell surface, this new receptor will capture labeled chelates and ultimately provide an image of the cluster of transformed cells that express the receptor. Phase 2 will focus on development of new products that apply this technology to a useful set of metallic elements and imaging techniques. PROPOSED COMMERCIAL APPLICATION: High-resolution imaging of gene expression in cancer cells is important to the future science and technology of cancer treatment. The molecular tools that we prepare will allow the physical properties of metallic elements to be employed in new ways. They will find uses in a variety of high-technology imaging applications, in both research and (ultimately) clinical applications.
