There is a great need to study disruptions to redox and oxygen homeostasis in cancer because the presence of hypoxic cores in tumors have been correlated to chemotherapy and radiation therapy resistance, metastases, and overall cancer longevity. The long-term goal of the research project is to develop redox-responsive probes that target unmet needs in the study of hypoxia in cancer. The overall objectives of this research project are (1) to synthesize and characterize two EuII-containing probes tethered to a paramagnetic shift agent and (2) to study the potential of these probes for use in redox-responsive multi-modal imaging using both relaxivity measurements and paramagnetic-shift enhancement. The rationale that underpins the proposed research is that the T1-weighted signal will only be present when EuII is in reducing environments, and the paramagnetic signal will only be present once EuII is oxidized to EuIII in oxidizing environments, thus rendering the agent redox- responsive for both imaging modalities. The expected outcome of this proposal is the successful synthesis and characterization of two imaging agents that differ in Eu coordination environments. This outcome is expected to have a positive impact because there is a critical need for new redox-responsive probes. The objectives of the proposal are expected to be achieved by pursuing two specific aims: (1) to synthesize and characterize a EuII- containing cryptate linked to a DyIII-containing paramagnetic-shift agent and (2) to synthesize and characterize a EuII-containing tetraamide glycinate complex linked to a DyIII-containing paramagnetic-shift agent. The resulting new complexes will be significant because they are expected to enable monitoring of changes in redox environments resulting from therapies, consequently aiding in treatment development and selection as well as increasing the basic understanding of the relationship between redox homeostasis and human health. Furthermore, because redox homeostasis is relevant to the diagnosis, mechanistic understanding, and therapeutic outcome of cancer, this proposal is expected to maximize returns in many other investments of the NIH and is specifically pertinent to the NCI’s mission. The proposed research project was designed to aid Corbin in developing her skillset in synthetic chemistry to best prepare her for an independent career in academia, which is a significant goal of the fellowship training plan. The Allen Research Group in the Chemistry Department at Wayne State University is the perfect environment for this research because it is collaborative, innovative, and set up with all the equipment Corbin will need to complete her research, including state-of-the-art instrumentation. In addition to the proposed research project, the training plan also includes professional development opportunities, training in the responsible conduct of research, and attending international scientific meetings.