Gadolinium-based MRI contrast agent effects on calcium signaling and actin-dependent cell functions

Since their first use in 1988, gadolinium-based magnetic resonance imaging (MRI) contrast agents (GBCAs) have been commonly and frequently applied for clinical MRI tests. The belief was that gadolinium is flushed out from the body within several hours post-administration and is entirely safe for the patient. However, studies of the last decade showed that gadolinium accumulates in cells and tissues for many years. Such findings triggered the U.S. Food and Drug Administration (FDA) drug safety warnings and new recommendations to minimize repeated GBCA imaging when possible. In this mini-review, we describe ours and other studies on the effect of gadolinium retention on calcium signaling, actin cytoskeleton dynamics, and actin-related cell functions and structures. Because little information exists on the effects of GBCAs on immune cells, we describe here our novel findings showing that gadolinium ions, similar in size to calcium ions, may affect processes regulated by calcium, such as actin-related pathways. We showed that GBCA Dotarem causes macrophage elongation, disrupts organelle positioning, and changes the expression of inflammatory factors. These results indicate that GBCAs may affect patients' immune responses, which would be especially harmful to immunocompromised patients.