This project is designed to carry out the development and characterization of oxygen-sensitive paramagnetic materials for use in viable biological systems and to facilitate their use by the potential user community. The proposed studies will build on the progress made during the initial six years of the PPG. We will collaborate closely with Projects II & III, developing and making available optimized paramagnetic materials, including thorough characterization of their biological interactions. The variables studied will include the type of paramagnetic material, the effects of different type of preparations, and the effect of placement into different organ systems. Different materials and/or preparations of the same types of materials will be developed and tested for specific uses, especially for studies in systems with low pO2 (tumors and ischemic tissues) and organs with relatively high pO2 (e.g. brain). There will be special emphasis on the development of capabilities to make measurements at multiple sites and multiple measurements from a single site. In collaboration with Project III we will thoroughly pursue the development of coated paramagnetic materials including steps that will facilitate the use of EPR oximetry in clinical medicine. This project also will carry out studies of the effects of experimental procedures on the oxygen in tissues, information that is essential for any study of oxygen-dependent processes. We also will systematically relate measurements to PtO2 with EPR oximetry to those of other techniques that already are widely available. A modest but important addition for this period will be the development of nitroxides for measuring pO2 in the vascular system for correlative studies with EPR oximetry that is based on particulates. The achievement of the goals for this grant period should result in the availability of optimized oxygen sensitive paramagnetic materials suitable for repeated and accurate measurements of pO2 in living systems and the information needed to use these materials and to interpret the results appropriately, including the limitations as well as the advantages of the measurements that are made. The availability of these materials and the background information on their use is anticipated eventually to have a positive effect on understanding and enhancing treatment of the many pathophysiologies whose mechanisms include changes in pO2 (e.g. cancer, ischemia-reperfusion injury in organs such as brain and heart, sepsis, and wound healing).
