학술논문
Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study.
Document Type
Academic Journal
Author
Haase T; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Ludwig A; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charitéplatz 1, 10117 Berlin, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10117 Berlin, Germany.; Stach A; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charitéplatz 1, 10117 Berlin, Germany.; Mohtashamdolatshahi A; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Hauptmann R; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Mundhenk L; Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163 Berlin, Germany.; Kratz H; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Metzkow S; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Kader A; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Department of Diagnostic and Interventional Radiology, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.; Freise C; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Mueller S; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Experimental Neurology, Center for Stroke Research Berlin (CSB), Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Charité 3R|Replace, Reduce, Refine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.; Stolzenburg N; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Radon P; Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany.; Liebl M; Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany.; Wiekhorst F; Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany.; Hamm B; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Taupitz M; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.; Schnorr J; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.; Department of Radiology, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101610216 Publication Model: Electronic Cited Medium: Print ISSN: 2079-4991 (Print) Linking ISSN: 20794991 NLM ISO Abbreviation: Nanomaterials (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2079-4991
Abstract
Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not yet been studied. This study aimed to investigate the effect of multiple intravenous injections of VSOPs in atherosclerotic mice. Taurine-formulated VSOPs (VSOP-T) were repeatedly intravenously injected at 100 µmol Fe/kg in apolipoprotein E-deficient (ApoE KO) mice with diet-induced atherosclerosis. Angiographic imaging was carried out by in vivo MRI. Magnetic particle spectrometry was used to detect tissue VSOP content, and tissue iron content was quantified photometrically. Pathological changes in organs, atherosclerotic plaque development, and expression of hepatic iron-related proteins were evaluated. VSOP-T enabled the angiographic imaging of heart and blood vessels with a blood half-life of one hour. Repeated intravenous injection led to VSOP deposition and iron accumulation in the liver and spleen without affecting liver and spleen pathology, expression of hepatic iron metabolism proteins, serum lipids, or atherosclerotic lesion formation. Repeated injections of VSOP-T doses sufficient for MRA analyses had no significant effects on plaque burden, steatohepatitis, and iron homeostasis in atherosclerotic mice. These findings underscore the safety of VSOP-T and support its further development as a contrast agent and molecular imaging tool.