Transition metal PARACEST MRI contrast agents: Fe(II), Ni(II), Co(II)

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With support from the Chemical Measurement and Imaging Program, Prof. Janet Morrow and her group at the University at Buffalo, State University of New York are developing new magnetic resonance imaging (MRI) contrast agents that utilize the biologically relevant metal ions, Fe(II), Co(II) and Ni(II). Coordination complexes of these transition metal ions produce contrast through paramagnetic chemical exchange saturation transfer (PARACEST). The primary goal is to design PARACEST agents with exchangeable proton resonances shifted far from those of bulk water ( 100 ppm) and to optimize exchange rate constants for enhanced contrast. Second, the extensive coordination chemistry and accessibility of different oxidation states of transition metal elements facilitates the design of contrast agents that are responsive to biological environment. For example, PARACEST agents that are switched on by a change in pH or redox potential will be prepared. CEST NMR experiments and CEST MRI experiments on a 4.7 T scanner will be conducted with the goal of developing imaging protocols for optimizing contrast. Experiments for undergraduates and high school teachers and their students will be developed to make the connection between magnetic properties of metal ions and MR imaging. MRI is a clinically important diagnostic procedure, with about half of MRI scans using contrast agents in order to better image differences in tissue. The development of contrast agents that switch on in tissue which has characteristics of a disease state could be extremely useful for improved diagnostics and treatment. The proposed research will focus on the development of such switchable contrast agents that contain iron, cobalt or nickel. These metal ions, especially iron, may be potentially safer than currently utilized rare earth contrast agents because they may be metabolically recycled. This project will develop the coordination chemistry and imaging protocols that are necessary to tap into the significant and unexplored potential of these new contrast agents for imaging applications.