Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field Magnetic Reso

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There is a great need for positive contrast agents for ultra-high field strength (e7 T) magnetic resonance imaging (MRI) to enable increased spatial resolution and sensitivity to disease states in both preclinical and clinical research. Our long-term goal is to develop positive contrast agents for ultra-high field strength MRI to fill this void in diagnostic medicine by focusing on EuII complexes that are among the most promising areas of study. The overall objective of this application is to establish the groundwork necessary for translation of our new EuII-based complexes into useful contrast agents by maximizing stability, optimizing imaging properties, and evaluating toxicity. The rationale that underpins the proposed research is that EuII can be stabilized against oxidation and rendered non-toxic in vivo through ligand modification and formulation with antioxidants as we have recently demonstrated. The expected outcome of this proposal is the establishment of EuII-based complexes for use as contrast agents in ultra-high field strength MRI. This outcome is expected to have a positive impact by contributing to the NIH's mission in the diagnosis of human diseases. We plan to achieve the objective of the proposal by pursuing three specific aims: (1) to chemically enhance the stabilities and imaging-relevant parameters of our EuII-containing complexes; (2) to characterize the toxicity of our EuII- containing complexes; and (3) to characterize the in vivo imaging properties of our EuII-containing complexes. The new EuII-based probes will be significant because they are expected to enable diagnostic images to be acquired at ultra-high field strengths with higher resolution in less time than those currently acquired at clinical field strengths. Furthermore, because ultra-high field strengths are commonplace in NIH-supported preclinical research, this proposal is expected to maximize returns in the many other investments of the NIH related to MRI.