How to determine free Gd and free ligand in solution of Gd chelates. A technical note

Gd(III) chelates are often used as reporting probes in magnetic resonance imaging applications. Their use relies on the assumption that their high stability ensures against the release of free ligand and free Gd(3+) ions, which are both highly toxic to living systems. The presence of free Gd(3+) ions may have a profound effect on the contrast in the MR image as they may form highly hydrated, macromolecular complexes endowed with very high relaxivity thus providing erroneous information on the extent of the contrast effect induced by the given reporting probe. Although the stability of a given complex may be high enough, the complexation step could not have been completed. Therefore any Gd complex preparation has to be carefully checked for the content of free ligand and free metal ions. Herein the currently used procedures that allow an assessment of the amounts of free metal ions and free ligand in a solution of a given Gd complex are described in detail.