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 Fe^II 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 Fe^II 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. Paramagnetic metal ions are important for the development of MRI contrast agents that function through chemical exchange saturation transfer (CEST or paraCEST). Recent work shows that Fe^II paraCEST MRI contrast agents are promising new candidates to add to the current repertoire of lanthanide(III) complex contrast agents.