Detection of Gd-based contrast agent in the skin of a patient eight years after administration

Nephrogenic systemic fibrosis (NSF) is a rare disease that is only diagnosed in patients with impaired renal failure after application of Gd-based contrast agents. Characteristics of the potentially fatal disorder NSF are swelling and hardening of the skin as well as the formation of brawny thickening at the extremities. First cases of this disease were observed in 2000 and in 2006 the relationship between NSF and the administration of so-called linear GBCA to renal failure patients was proposed. In 2009, researchers proposed that transmetallation of the Gd-based contrast agent resulting in the release of free Gd³⁺, to be the critical process for the toxic action. However, the pathogenesis is still not completely understood.

Researchers from the University of Münster now used a unique combination of elemental bioimaging and speciation analysis to study the presence of gadolinium compounds in skin biopsy samples of a 25-year-old female with NSF symptoms.

Laser ablation-ICP-MS was used to map the distribution of gadolinium and other elements within the skin biopsies and microwave digestion followed by ICP-MS was used to determine the total gadolinium concentration.

The total gadolinium concentration in the tissue was found to be between 3.02 and 4.58 mg/kg for three biopsy samples. Much higher concentrations of gadolinium, namely, from 50 mg/kg to approximately 400 mg/kg, were detected in three individual areas in the tissue section of a NSF patient by LA-ICP-MS. Furthermore, a good correlation between the distributions of phosphorus and gadolinium suggests the presence of GdPO₄ deposits in the tissue section.

The researchers summarized that significant Gd deposits in the tissue samples were observed even years after delivery of the contrast agent, thus allowing an unambiguous diagnosis of NSF for the patient.

The researchers then applied speciation analysis by using HILIC-ICP-MS to aqueous extracts of skin biopsies in order to look for the originally applied Gd-based contrast agents. Despite the fact that the administration of the GBCA in connection with MRI of the patient took place eight years prior to the skin biopsy, the highly sensitive technique allowed to detect the macrocyclic GBCA Gd-HP-DO3A besides two other non-identified Gd-compounds.

The authors conclude that the presence of unidentified Gd-species call for further studies regarding speciation analysis to gain information about species transformation during the course of NSF development.

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October 16, 2017: Gadolinium found in the brain of a patient two years after having received a Gd-based contrast agent for medical imaging
July 29, 2017: EMA Issues Final Opinion Limiting Gadolinium Contrast Agents in Body Scans
May 23, 2017: FDA identifies no harmful effects to date with brain retention of gadolinium-based contrast agents for MRIs
March 11, 2017: European Medicines Agency recommends to pull linear Gadolinium-based MRI contrast agents from market 
April 10, 2016: New Studies Question Safety of MRI Contrast Agents
August 13, 2015: FDA investigating risk of gadolinium contrast agent brain deposits
March 4, 2015: Detection of Gd-based contrast agent in the skin of a patient eight years after administration
October 29, 2012: Identification and quantification of potential metabolites of Gd-based contrast agents