3.6 MRI contrast agents
MRI contrast agents enter some types of tissue in preference to others, interacting with the water, reducing the relaxation times (increasing 1/ and 1/) of protons in these tissues to differing extents and thus increasing the signal intensity.
Based on your experience of coordination chemistry, describe how water can interact with a metal ion.
Water molecules can act as ligands and bind directly to a metal in an inner-sphere coordination. Other water molecules are bound further away from the metal ion, often hydrogen-bonded to one of the ligands; this is outer-sphere coordination (Figure 13). Although not interacting directly with the metal, bulk water is also included here.
Looking again at Figure 13, you can see that protons on the outer-sphere water may also effectively become inner sphere by hydrogen-bonding to an inner-sphere ligand.
In the inner sphere, water molecules will be influenced more by the magnetic field of the metal ion than water molecules in the outer sphere. But the latter are in a good position to interact with protons in the bulk of the surrounding tissues.
As mentioned earlier, practical contrast agents tend to be based on the lanthanide metal gadolinium.
What oxidation state will gadolinium cations exhibit?
As is the case for the lanthanides in general, +3 is the most common oxidation state.
As you saw previously, gadolinium(III) has a high magnetic moment (μ = 8.0 μB due to seven unpaired electrons), and it’s this high moment which makes it especially effective at modifying the relaxation processes of nearby protons.
But that’s not the whole story.
For a contrast agent to affect the relaxation rates of protons in tissues, there must be a dynamic exchange of water molecules between the inner sphere, the outer sphere and uncomplexed bulk water molecules. This exchange must be fast relative to the proton relaxation rate.
During MRI, a patient is injected with about a gram of gadolinium, but in aqueous solution the metal exists as , which, as you’d expect for a heavy metal, is highly toxic.
What challenge does this present to a chemist working in this field?
This means researchers have had to find suitable ligands that form complexes that remain bonded while in the body and are excreted intact. This will be considered in more detail in the next section.