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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.

The new study:
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.

a) Microscopic image of the investigated skin section of a NSF patient.
b) LA-ICP-MS distribution map for Gd in the same skin section
c) HILIC-ICP-MS chromatograms of the sample extract

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.

The cited study:

Marvin Birka, Kristina S. Wentker, Elke Lusmöller, Brigit Arheilger, Christoph Alexander Wehe, Michael Sperling, Rudolf Stadler, and Uwe Karst, Diagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis, Anal. Chem., Article ASAP, DOI: 10.1021/ac504488k, Publication Date (Web): February 23, 2015

Used Instrumentation:

Thermo Scientific iCAP QC ICP-MS
Teledyne CETAC LSX-213
Shimadzu LC-10 ADVP HPLC pumps


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Related EVISA News

September 15, 2010: US FDA Announces Gadolinium-Based MRI Contrast Agent Warning
March 25, 2010: Publication on the separation of Gd-based contrast agents awarded
May 4, 2009: Gadolinium speciation analysis in search for the cause of nephrogenic systemic fibrosis (NSF)
April 17, 2009: Gadolinium-based MRI contrast agents found intact in the outlet of a waste water treatment plant

last time modified: March 4, 2015

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