This proposal addresses development of new imaging technology for noninvasive quantitative measurement of apoptosis in vivo. Apoptosis is genetically defined cell death. Understanding the role of apoptosis is critical to the development of new molecular-based therapeutic modalities. An apoptosis-imaging agent could be used to modify therapy for cancer patients, and to monitor cardiac transplant patients. Our group is currently participating in an apoptosis imaging trial, employing Annexin-V labeled with Technetium-99m. We propose to label Annexin-V with a positron emitter appropriate for PET scanning. Potential advantages of PET include improved spatial resolution and quantitation, which will be important for monitoring early cancers and for cardiac studies. Phase I research will consist of development of a procedure for effective radiofluorination of Annexin-V. The main goals of Phase I are: (1) the attainment of parameters (i.e., specific activity, and short preparation time) accepted in the industry as requirements for a useful PET imaging agent, and (2) demonstration of in vitro binding activity in classic models for apoptosis. Further Phase I work to assess biologic activity in chemotherapy-treated cultures of pediatric tumor cells will set the stage for subsequent animal testing. These later studies will employ PEM Technologies' proprietary PET-guided biopsy tools. PROPOSED COMMERCIAL APPLICATIONS: Development of radiotracers for PET is a high-growth area, with over $150 million invested annually for new production and R&D. The product of this proposal will aid noninvasive quantitative measurements as to the efficacy of molecular-based anticancer agents. The proposing company (PEM Technologies) offers proprietary platforms for cost-effective PET imaging and PET-guided biopsy
