Gadolinium accumulationDoes gadolinium accumulate in tissues after repeated doses?
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Yes. Although nearly all gadolinium is cleared from the circulation by renal excretion over the first several hours in patients with normal renal function, some free gadolinium always makes its way into tissues. The displacement of gadolinium from its chelation site occurs at least in part via the so-called transmetallation reaction, where it is bumped out by another cation (such as Zn+2 or Ca+2).
Recent papers have demonstrated that gadolinium accumulation with concomitant T1 shortening can be seen in the brains of patients who have received multiple doses of gadolinium contrast. The effect is most noticeable in the globus pallidi, thalami, pons, and dentate nuclei. The magnitude of the effect is proportional to the cumulative lifetime dose administered and occurs without renal or hepatic dysfunction. Research suggests the phenomenon is more common in linear agents with weaker chemical binding to free gadolinium than to macrocyclic agents with stronger binding. Visible changes on T1-weighted images may be present after as few as 4 exposures. An example is provided below.
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The patient shown right underwent 21 contrast-enhanced MR scans between 2002 and 2012 for a fourth ventricular tumor. Progressive high signal was noted on T1-weighted images in the dentate nuclei and globus pallidi over time, presumably due to gadolinium accumulation.
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1st MRI scan 2002
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22nd MRI scan 2012. Note high T1 signal in basal ganglia.
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Although deposition of gadolinium in the brain has garnered the most attention, even higher amounts have been shown to accumulate in liver, spleen, kidney and bone. However, subtle signal changes on T1-weighted MR images have not been reported in these organs.
As yet no documented short or long-term adverse affects are recognized from deposition of these small amounts of Gd in tissues. Indeed, trace amounts of many other heavy metals (e.g., mercury, lead, aluminum) also silently exist in the human body acquired from diet or the environment. I am not saying that gadolinium is good for you, but just because we can see it on MRI doesn't mean it is harmful.
The final answer is not in concerning which of the commercially available gadolinium-based contrast agents provides the least risk for tissue deposition. In late 2017 the European Medicines Agency issued a recommendation to suspend or limit use of a three linear agents throughout the EU: Omniscan®, Magnevist®, and MultiHance®. The US FDA has not recommended limiting these agents, but has issued an edict that patients be informed about these issues and given "Medication Guide" describing the potential risks of receiving each type of contrast material. An example of such a recently approved Medication Guide for MultiHance® can be downloaded here.
References
ACR Committee on Drugs and Contrast Agents. ACR Manual on Contrast Agents, 2023. American College of Radiology, 2022.
European Medicines Agency. EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans. 23 Nov 2017.
Hatje V, Bruland KW, Flegal AR. Increases in anthropogenic gadolinium anomalies and rare earth element concentrations in San Francisco Bay over a 20 year record. Environ Sci Technol 2016; (6-fold increase in the concentration of Gd in waters of SF Bay noted between 1993 and 2013. Not a toxic or human safety issue, but an interesting environmental side effect of medical gadolinium use)
Kanal E, Tweedle MF. Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology 2015; 275:630-634. (Editorial/review).
Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 2014; 270:834-841. (Landmark first report of Gd accumulation in brain).
McDonald RJ, McDonald JS, Dai D, et al. Comparison of gadolinium concentrations within multiple rat organs after intravenous administration of linear versus macrocyclic gadolinium chelates. Radiology 2017; 285:536-545.
McDonald JR, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015; 275:772-782.
McDonald RJ, McDonald JS, Kallmes DF, et al. Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 2017; 285:546-554. (Shows most of Gd is deposited in vascular endothelium although some makes it into brain cytoplasm and nuclei).
Radbruch A, Weberling LD, Kieslich PJ, et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 2015; 275:783-791. (More Gd deposition seen with linear agent gadopentate [Magnevist] than with macrocyclic agent gadoterate [Dotarem])
White GW, Gibby WA, Tweedle MF. Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 2006;41:272-278.
ACR Committee on Drugs and Contrast Agents. ACR Manual on Contrast Agents, 2023. American College of Radiology, 2022.
European Medicines Agency. EMA’s final opinion confirms restrictions on use of linear gadolinium agents in body scans. 23 Nov 2017.
Hatje V, Bruland KW, Flegal AR. Increases in anthropogenic gadolinium anomalies and rare earth element concentrations in San Francisco Bay over a 20 year record. Environ Sci Technol 2016; (6-fold increase in the concentration of Gd in waters of SF Bay noted between 1993 and 2013. Not a toxic or human safety issue, but an interesting environmental side effect of medical gadolinium use)
Kanal E, Tweedle MF. Residual or retained gadolinium: practical implications for radiologists and our patients. Radiology 2015; 275:630-634. (Editorial/review).
Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 2014; 270:834-841. (Landmark first report of Gd accumulation in brain).
McDonald RJ, McDonald JS, Dai D, et al. Comparison of gadolinium concentrations within multiple rat organs after intravenous administration of linear versus macrocyclic gadolinium chelates. Radiology 2017; 285:536-545.
McDonald JR, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015; 275:772-782.
McDonald RJ, McDonald JS, Kallmes DF, et al. Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 2017; 285:546-554. (Shows most of Gd is deposited in vascular endothelium although some makes it into brain cytoplasm and nuclei).
Radbruch A, Weberling LD, Kieslich PJ, et al. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 2015; 275:783-791. (More Gd deposition seen with linear agent gadopentate [Magnevist] than with macrocyclic agent gadoterate [Dotarem])
White GW, Gibby WA, Tweedle MF. Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 2006;41:272-278.
Related Questions
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Do all MR contrast agents carry the same risk of NSF?
Does retention of gadolinium in the body cause symptoms?