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Updated: Jun 28, 2025
Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging
Published on: December 4, 2016
Gadolinium retention effect on macrophages - a potential cause of MRI contrast agent Dotarem toxicity
Marta Halasa1,2, Ahmed Uosef1,2, Henry V Ubelaker1,2
1Transplant Immunology, The Houston Methodist Research Institute, 6670 Bertner Ave., Houston, TX, 77030, USA.
Abstract:
Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient's immune system and immune response-related processes.
Insights
Gadolinium from MRI contrast agents accumulates in macrophages, impairing immune cell function. Long-term gadolinium retention significantly reduces macrophage motility and alters key immune and fibrotic pathways, potentially harming patients.
Area of Science:
- Immunology
- Toxicology
- Biomedical Imaging
Background:
- Gadolinium-based contrast agents (GBCAs) like Dotarem are widely used in MRI.
- Gadolinium accumulates in organs and tissues, with potential long-term toxic effects.
- Previous studies show gadolinium retention in macrophages for at least 7 days post-exposure.
Purpose of the Study:
- To investigate the impact of gadolinium retention on macrophage function and molecular pathways.
- To assess the effects of 1-day and 7-day gadolinium exposure on macrophage behavior.
Main Methods:
- Macrophage cultures exposed to gadolinium for 1 and 7 days.
- Analysis of macrophage adhesion, motility, protein expression, and mRNA transcription.
- Focus on proteins and genes related to adhesion, fibrosis, and immune response.
Main Results:
- Seven-day gadolinium retention significantly decreased macrophage adhesion and motility.
- Dysregulated expression of proteins (Notch1, Jagged1, PAK1, Shp1, Smad3, TCF19) and chemokines (CXCL10, CXCL13).
- Altered mRNA expression of fibrosis genes (Col6a1, Fibronectin, MMP9, MMP12) and complete suppression of the M2 marker Arg-1.
Conclusions:
- Gadolinium retention in macrophages disrupts critical cellular functions and molecular pathways.
- Observed changes may negatively impact the patient's immune system and response.
- Further research is needed to understand the clinical implications of gadolinium-induced macrophage dysfunction.
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