MRI probes for sensing biologically relevant metal ions

Given the important role of metal ions in fundamental biological processes, the visualization of their concentration in living animals by repeatable, noninvasive imaging techniques, such as MRI, would be highly desirable. A large number of metal-responsive MRI contrast agents, the majority based on Gd3+ complexes, have been reported in recent years. The contrast-enhancing properties (relaxivity) of a Gd3+ complex can be most conveniently modulated by interaction with the sensed metal cation via changes in the number of water molecules bound directly to Gd3+ or changes in the size of the complex, which represent the two major strategies to develop metal sensitive MRI probes. Here, we survey paramagnetic lanthanide complexes involving Gd3+ agents and paramagnetic chemical exchange saturation transfer probes designed to detect the most important endogenous metal ions: calcium, zinc, iron and copper. Future work will likely focus on extending applications of these agents to living animals, as well as on exploring new ways of creating molecular MRI probes in order to meet requirements such as higher specificity or lower detection limits.