- Clinical Need
- Over 30 million contrast-enhanced (CE) MRI scans are done worldwide each year.
CE-MRI scans provide vital medical insight informing diagnosis and management of cancer, stroke, multiple sclerosis, cardiovascular disease, genetic disorders, and many other conditions.
- Current Technology
- All current MRI contrast agents are based on gadolinium, a rare earth element which is alien to biology. Gadolinium is a potent calcium antagonist and is highly toxic in its ionic form. Gadolinium-based contrast agents (GBCAs) utilize chelating ligands to bind the metal and render it less toxic for intravenous administration. Nevertheless even the most stable GBCAs release some gadolinium.
- Safety Issues
- In 2006 it was found that GBCAs trigger devastating nephrogenic systemic fibrosis (NSF) in renally impaired patients. Subsequently, deposition of gadolinium in bone, skin, and other organs was documented. In 2013 it was discovered that GBCAs cause cumulative gadolinium deposition in the brain of all patients regardless of renal function. Studies have shown that all GBCAs cause deposition of gadolinium in the brain, bone, and other organs of all patients.
- Regulatory Response
- The FDA instituted a boxed warning on all GBCAs in 2007, cautioning that they should not be used in renally impaired patients due to the risk of NSF. After the discovery of brain deposition of gadolinium, worldwide regulators responded with suspensions, restrictions, label changes, and safety warnings. There is continuing unease and uncertainty about GBCAs. Even the most stable GBCAs release gadolinium, which remains in the body. The long term biological activity of gadolinium – and consequent implications for patients – are not well understood.
- Patients and Physicians
- CE-MRI provides critical medical information which cannot be obtained using other methods. Patients and physicians face a dilemma: balancing the risks posed by GBCAs with the need for important diagnostic imaging. Patient care is impacted: without CE-MRI physicians cannot obtain vital information required for diagnosis and patient management decisions. Patients at greatest risk from GBCAs include renally impaired patients, pediatric patients, and patients who require repeat CE-MRIs. e.g. BRCA surveillance, multiple sclerosis, cancer, and chronic conditions.
- Environmental Impact
- Increasing use of CE-MRI has resulted in rapidly rising levels of gadolinium in water around major metropolitan areas. GBCAs enter the sewage system when they are excreted after CE-MRIs. GBCAs are not removed by standard waste water treatment methods: consequently the GBCAs remain in the clear water discharge from sewage treatment plants and are transferred to surface water. Unlike biocompatible elements, gadolinium has no established ecological cycle. The biological activity of the rising amount of gadolinium in the aquatic ecosystem and the consequences of gadolinium entering the drinking water supply are as yet undetermined.
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