Lanthanide chelates as magnetic resonance imaging contrast agents

Several chelates of Gd³⁺ are being evaluated for use as magnetic resonance imaging (MRI) contrast agents. This trivalent lanthanide has become the ion chosen for many MRI applications because of its large magnetic moment, long electron-spin relaxation time, and favorable water coordination number and exchange rates. The characteristics of those gadolinium chelates which appear to be safe for use in humans include thermodynamic stability and/or kinetic inertness and a low net negative charge at pH 7.4. Two of the most widely used complexes to date include Gd(DTPA)^2- and Gd(DOTA)^-. These non-specific blood pool agents distribute throughout the extracellular spaces (both intra- and extravascular) before being cleared through the kidneys. Chelates may also be covalently attached to a macromolecule to restrict the paramagnetic ion in the intravascular space or target it to a particular organ or cell type. Monopropylamide derivatives of DTPA and DOTA, which serve as models for chelate-conjugated proteins, form considerably less stable complexes with Gd³⁺ without the expected increase in inner-sphere water molecules. The properties of the linear and macrocyclic chelates are compared, and those factors which yield the greatest MRI contrast per dosage of Gd³⁺ are discussed.