8 To answer to the need for safer MRI contrast agents, several approaches have been proposed in the recent years. 6, 7 These concerns prompted the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) to recommend the suspension of the marketing authorities for four linear GBCAs in March 2017. 5 Recently, several studies demonstrated that upon repeated administration of GBCAs, their deposition in central nervous system structures of patients with normal renal functions occurs. 3, 4 Moreover, cerebral accumulation of gadolinium in patients with preexisting renal dysfunction can also trigger transient signs of neurological disorders. Apart from minor side effects during administration, the use of GBCAs is also accompanied by an increased risk to renally impaired patients because of gadolinium retention in liver, spleen, heart, skin, kidneys, and bladder, which can lead to nephrogenic systemic fibrosis. Besides, GBCAs are often associated with side effects, usually due to the release of toxic gadolinium ions. However, despite their acceptable imaging properties as bright contrast agents, their functional imaging possibilities are very limited. 2 Gadolinium-based contrast agents (GBCAs) are the current “gold standard” in MRI. Since these agents are applied intravenously, certain prerequisites must be fulfilled, including low toxicity, good biocompatibility, suitable imaging properties, blood stability, as well as a defined biodistribution and elimination. 1 In order to significantly enhance the contrast and to extend the application area of MRI, contrast agents are required. It also possesses acceptable spatial resolution and soft tissue contrast. One of the most important imaging tools in this regard is magnetic resonance imaging (MRI), which utilizes magnetic fields instead of ionizing radiation to excite protons. The development of suitable imaging modalities is one of the key requirements to detect diseases at the earliest possible stage, select an appropriate dose and timing of the therapy, and monitor the disease progression. Keywords: CARPA, cross-linking, irritation potential, MRI, SPION, storage stability Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPION Dex indicated the absence of hypersensitivity reactions.Ĭonclusion: These results emphasize the exceptional safety of SPION Dex, setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development. Cell uptake studies of ultra-small (30 nm) SPION Dex confirmed their internalization by macrophages, but not by non-phagocytic cells. Results: Independent of their size, SPION Dex displayed no irritation potential in a chick chorioallantoic membrane assay. Furthermore, we performed an extensive analysis of the particles’ storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Methods: In the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPION Dex) for biomedical applications in terms of safety and biocompatibility. Harald Unterweger, 1 László Dézsi, 2,3 Jasmin Matuszak, 1 Christina Janko, 1 Marina Poettler, 1 Jutta Jordan, 4 Tobias Bäuerle, 4 János Szebeni, 2,3 Tobias Fey, 5 Aldo R Boccaccini, 6 Christoph Alexiou, 1 Iwona Cicha 1ġENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany 2Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary 3SeroScience Ltd., Budapest, Hungary 4Institute of Radiology, Preclinical Imaging Platform Erlangen, Universitätsklinikum Erlangen, Erlangen, Germany 5Institute of Glass and Ceramics, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany 6Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germanyīackground: Rising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents.
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