In this project funded by the Chemical Structure, Dynamic & Mechanism B and the Chemical Measurement & Imaging Programs of the Chemistry Division, Professor Janet R. Morrow of the Department of Chemistry at the University at Buffalo, State University of New York is developing new classes of iron (Fe) complexes as magnetic resonance imaging (MRI) contrast agents. The goal of this research is to obtain new iron-based agents that produce effective MRI contrast at the field strengths found in the newest MRI scanners. Iron is a biologically relevant metal ion that may be an alternative to the currently used gadolinium, which has tolerance issues in imaging. The project lies at the interface of organic and inorganic chemistry, as well as physiology and imaging physics and is therefore well suited to the education of scientists at all levels. Professor Morrow has a strong record of educating a diverse group of graduate and undergraduate students. Outreach activities involving K-12 students and their science teacher are also be part of the funded project.
Macrocyclic Fe(III) complexes are being developed as MRI contrast agents with the goal of obtaining agents that produce effective T1 contrast at the clinically relevant magnetic field of 3 Tesla (T). The complexes contain highly stabilized Fe(III) centers that do not produce reactive oxygen species. Complexes that contain one bound water or no water ligands are to be studied to assess the effect of outer versus innersphere water on T1 relaxivity. A second emphasis is to develop Fe(III) contrast agents that change paramagnetic properties with temperature and pH. These spin state changes interconvert Fe(III) paramagnetic CEST (Chemical Exchange Saturation Transfer) agents and T1 contrast agents. EPR (Electron paramagnetic resonance) and Mossbauer spectroscopy will be used for characterization of the complexes. To study the magnetic field strength dependence of relaxivity, the complexes will be studied on MRI scanners at 1.5 T, 3.0 T and 4.7 T. A nuclear magnetic resonance dispersion spectrum will be obtained for selected Fe(III) complexes. The most effective Fe(III) contrast agents will be studied and compared to Gd(III) contrast agents in biological samples.
