Can gadolinium be re-chelated in vivo? Considerations from decorporation therapy

Gadolinium (Gd) and Gd-based contrast agents (GBCAs) have been observed to deposit in tissues of patients following contrast enhanced MR imaging procedures. A conservative approach for chelation therapy of this toxic metal dictates the assumption that minimal intact GBCAs are present. Currently the extent to which these deposits are primarily de-chelated Gd remains uncertain, prevailing knowledge suggests that for linear agents much of the Gd is de-chelated, while for the macrocyclic agents, the Gd may be still largely chelated. To extract Gd from tissues and facilitate its release, chelation therapy should be both safe and effective. Here we discuss chelation therapy as it relates to Gd deposition. The principles of chelation are reviewed, initially with reference to ligand stability in complex biological fluids. A model of decorporation and how it relates to elimination of Gd deposits is also reviewed. When more is learned about Gd deposition, optimal removal strategies must be developed using basic thermodynamic and kinetic principles.