Dechelation (Transmetalation): Consequences and Safety Concerns With the Linear Gadolinium-Based Contrast Agents, In View of Recent Health Care Rulings by the EMA (Europe), FDA (United States), and PMDA (Japan)

The issue of dechelation (transmetallation) in vivo after administration of the linear gadolinium-based contrast agents, and potential safety concerns, is considered on the basis of an extensive, focused literature review. Early indications of potential problems included the high level of excess ligand used in the formulation of 2 agents (indeed the 2 least stable thermodynamically) and interference with laboratory tests when blood was drawn from patients relatively soon after administration of these same agents. The advent of nephrogenic systemic fibrosis in the late 2000s raised additional major concerns. The correlation in 2014 of dentate nucleus hyperintensity on precontrast T1-weighted scans with multiple prior injections of linear gadolinium chelates, in patients with normal renal function, has driven subsequent research concerning dechelation of these agents in vivo. Unexpectedly high levels of gadolinium in the bone, skin, and liver have been found long term after administration, in animal models and in humans, although the latter data are limited. Bone may serve as a long-term reservoir, with a residual excretion phase for gadolinium after intravenous injection of the linear agents due to a subsequent slow release from bone. Many different patient populations could be vulnerable and potentially later develop clinical symptoms, although at this stage there are only limited data and small retrospective uncontrolled studies. Possible vulnerable populations include chil...
Source: Investigative Radiology - Category: Radiology Tags: Review Article Source Type: research