A recent study by Murata et al, “Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results from 9 Patients with Normal Renal Function”, adds to the mounting evidence of gadolinium deposition and retention in patients with normal renal function.  The study, published online ahead of print in Investigative Radiology, found that “Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function”.  The authors noted that, “Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two”.

The linear gadolinium-based contrast agents (GBCAs) most frequently associated with NSF were designated as Group 1 agents by the FDA in 2010.  Those agents are gadodiamide (Omniscan), gadoversetamide (OptiMARK), and gadopentetate (Magnevist).  The linear protein binding agents include gadobenate dimeglumine (MultiHance), gadoexetate (Eovist), and gadofosveset (Ablavar). 

For this study, tissue samples were collected from nine decedents undergoing autopsy that had received one or more injections of a single type of non-Group 1 GBCAs.  Patients who had never had an MRI or had undergone only noncontrast MRI were included as control subjects.  Of the nine decedents with exposure to contrast, 5 received gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), 2 received gadobutrol (Gadovist; Bayer Healthcare, Whippany, NJ), and 1 each had gadobenate (MultiHance; Bracco Diagnostics), and gadoxetate (Eovist; Bayer Healthcare).  Gadolinium was found with all agents in all brain areas sampled with the highest levels in globus pallidus and dentate.  Bone levels of gadolinium measured 23 times higher (median) than brain levels.  In controls, gadolinium levels in the brain were at or below limits of measurement by inductively coupled plasma mass spectrometry (ICP-MS).

The authors concluded that further studies are needed to determine the form(s) of gadolinium deposited for various GBCAs and implications for any possible adverse health effects.  They also noted that bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker.

Interestingly, this is not the first study to confirm gadolinium retention in bone removed from patients with normal renal function.  In 2004, Gibby et al first reported Gd retention in bone tissue collected from patients that received either the linear agent Gd-DTPA-BMA (Omniscan) or the macrocyclic agent Gd-HP-DO3A (ProHance).

Here we are 12 years later and we still do not know what the long-term health implications are for patients exposed to gadolinium-based contrast agents.  What happens when gadolinium is released from patients’ bones over the course of many years?

Sharon Williams

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Murata, N., Gonzalez-Cuyar, L. F., Murata, K., Fligner, C., Dills, R., Hippe, D., & Maravilla, K. R. (9000). Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. Investigative Radiology, Publish Ah. Retrieved from http://journals.lww.com/investigativeradiology/Fulltext/publishahead/Macrocyclic_and_Other_Non_Group_1_Gadolinium.99224.aspx

Gibby, W. A., Gibby, K. A., & Gibby, W. A. (2004). Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Investigative Radiology, 39(3), 138–42. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15076005