“SPIONdex/USPIOdex particles represent a suitable candidate for new-generation MRI contrast agents, offering the possibility of sequential imaging at a low risk of hypersensitivity reactions”
Magnetic resonance imaging (MRI) contrast agents are used in MRI to enhance the sensitivity and/or specificity of the technique and improve the visibility of bodily organs and vasculature.
Of the approximate 60 million MRI procedures performed annually worldwide, most are carried out using gadolinium-based contrast agents (GBCAs). However, due to the emergence of convincing evidence that gadolinium accumulates and deposits in brain tissue, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency has now recommended that the use of most intravenous linear GBCAs be suspended, which has led researchers to search for alternative MRI contrast agents.
One such alternative that has been used for MRI scans of the liver, lymph nodes, cardiovascular system and intestines is superparamagnetic iron oxide nanoparticles (SPIONs).
SPIONs are usually around 100nm in size and are composed of an oxide crystal core coated with an organic dextran or carboxydextran shell. These particles are retained by the reticuloendothelial system (RES) − the network of cells and tissues involved in phagocytosis that are found throughout the body, particularly in the blood, liver, lungs, spleen, lymph nodes, bone marrow and general connective tissue.
However, safety concerns have also arisen about the use of SPIONs as MRI contrast agents, particularly regarding hypersensitivity reactions, and no intravenous iron oxide-containing agents are currently available on the market.
At the University Hospital Erlangen in Germany, Harald Unterweger and colleagues have been performing immuno-safety and biocompatibility studies of a newly developed dextran-coated SPION called SPIONdex.
The team used Bruker’s D8 Advance X-ray diffraction system to determine the crystalline phase of SPIONdex and they performed in vivo ultra-high-field MRI using Bruker’s 7T ClinScan and 7T Pharmascan systems to characterize the nanoparticles.
In vitro experiments showed that SPIONdex possessed excellent hemocompatibility and did not trigger complement or platelet activation, hemolysis, plasma coagulation or leukocyte procoagulant activity.
Previously, it has been shown that pigs are highly sensitive to infused nano-formulations. To find out whether SPIONdex could induce hypersensitivity, the researchers intravenously administered the nanoparticles in a pig model and analysed complement activation-related pseudoallergy (CARPA). They found that SPIONdex did not induce CARPA, even when administered at a relatively high dose (5mg Fe/kg).
Studies have also previously shown that, depending on their size and coating, SPIONs can circulate for prolonged periods and trigger undesirable side effects upon injection. The ability to manipulate the composition, size and shape of SPIONs is therefore highly desirable and much research has been carried out into their synthesis and surface modification in efforts to yield desirable properties.
To assess the effects that size reduction would have on the biocompatibility of SPIONdex, Unterweger and team also carried out size-tunability studies. In vitro and ex vivo assays demonstrated that by changing synthesis parameters, particle size could be reduced to between 20 and 30nm, without this having any deleterious effects on hemo- and biocompatibility, thereby underscoring the potential of SPIONdex for organ/application-dependent adaptation.
The authors say their findings suggest that with their exceptional biocompatibility, low immunogenicity, superb safety profile and size-tunability, SPIONdex may present an opportunity for a new generation of MRI contrast agents.
Contact Bruker to learn more about how Bruker technology has been used to identify new contrast agents.
Unterweger, H et al. Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging. International Journal of Nanomedicine 2017;12:5223–5238. doi: 10.2147/IJN.S138108