The Development of Iron(II) Complexes as ParaCEST MRI Contrast Agents

Magnetic resonance imaging (MRI) is a powerful imaging modality for visualizing anatomical soft tissue using nonionizing radiation. Compared with other molecular imaging methods such as optical, nuclear, and ultrasound, sensitivity is limited but can be improved through development of chemical agents which enhance MRI contrast. MRI Contrast agents that function through paramagnetic chemical exchange saturation transfer (paraCEST) are currently being investigated as an alternative to T1 and T2 contrast agents. These agents may be designed as imaging probes which are intrinsically responsive to pH and temperature. Trivalentlanthanide complexes have dominated the relatively young field of paraCEST for just over a decade. Recently, high spin FeII complexes containing labile amide and amino protons which chemically exchange with bulk water have emerged as viable additions to the repertoire of paraCEST agents. This microreview will provide an overview of some considerations when designing paraCEST contrast agents which incorporate high spin FeII as the paramagnetic metal center. Important factors such as paramagnetic relaxation and hyperfine shifts, spin state, coordination, oxidation state, and stability will be discussed in regard to transition metal ion paraCEST contrast agent design.