Ultrasmall superparamagnetic iron oxide nanoparticles coated with fucoidan for molecular MRI of intraluminal thrombus.

AIM We have designed ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles associated with fucoidan (USPOI-FUCO), a natural sulfated polysaccharide with high affinity for activated platelets, to visualize by MRI arterial thrombi. MATERIALS & METHODS USPIOs were prepared and sizes, zeta-potentials and relaxivities were measured. Elastase perfusion in the infrarenal aorta of Wistar rats induced intraluminal thrombus. They were scanned on 4.7 T MRI before and after injection of USPIO-FUCO or USPIO coated with anionic dextran. RESULTS Surface plasmon resonance evidenced that fucoidan and USPIO-FUCO bind in vitro to immobilized P-selectin. All intraluminal hyposignals detected by MRI after injection of USPIO-FUCO on animals (13 out of 13) were correlated by histology with thrombi, whereas none could be identified with control USPIOs (0 out of 7). No signal was seen in absence of thrombus. Thrombi by MRI were correlated with P-selectin immunostaining and USPIO detection by electron microscopy. CONCLUSION In vivo thrombi can thus be evidenced by MRI with USPIO-FUCO.

[1]  G. Frija,et al.  Superparamagnetic iron oxides as positive MR contrast agents: in vitro and in vivo evidence. , 1993, Magnetic resonance imaging.

[2]  Henrik S. Thomsen,et al.  Recent hot topics in contrast media , 2011, European Radiology.

[3]  Jean-Baptiste Michel,et al.  Thrombus versus Wall Biological Activities in Experimental Aortic Aneurysms , 2009, Journal of Vascular Research.

[4]  Jean-Baptiste Michel,et al.  Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans , 2010, Cardiovascular research.

[5]  A. Kondo,et al.  Improved method for fluorescence labeling of sugar chains with sialic acid residues. , 1990, Agricultural and biological chemistry.

[6]  Z. Fayad,et al.  Magnetic Resonance Molecular Imaging of Thrombosis in an Arachidonic Acid Mouse Model Using an Activated Platelet Targeted Probe , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[7]  D. Buxton,et al.  Clinical Implications of Molecular Imaging Research Molecular Imaging of Aortic Aneurysms Animal Studies , 2022 .

[8]  V. Fuster,et al.  In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging. , 2011, Journal of the American College of Cardiology.

[9]  P. Merlet,et al.  99 mTc-Annexin-V Functional Imaging of Luminal Thrombus Activity in Abdominal Aortic Aneurysms , 2006 .

[10]  Fabien Hyafil,et al.  Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta: Relationship Between Signal Loss and Macrophage Infiltration , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[11]  Hisao Ikeda,et al.  Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. , 2002, Journal of the American College of Cardiology.

[12]  J. Deux,et al.  Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[13]  Calum Gray,et al.  Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide: A Pilot Study , 2011, Circulation. Cardiovascular imaging.

[14]  I. Bakunina,et al.  Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds , 2008, Biotechnology journal.

[15]  Martin J Graves,et al.  The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. , 2009, Journal of the American College of Cardiology.

[16]  横山 晋二,et al.  Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates , 2005 .

[17]  René M. Botnar,et al.  In Vivo Magnetic Resonance Imaging of Coronary Thrombosis Using a Fibrin-Binding Molecular Magnetic Resonance Contrast Agent , 2004, Circulation.

[18]  Y. Castier,et al.  Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats , 2011, PloS one.

[19]  Toxicological evaluation of fucoidan from Undaria pinnatifidain vitro and in vivo , 2010, Phytotherapy research : PTR.

[20]  Y. Huo,et al.  P-selectin glycoprotein ligand-1 plays a crucial role in the selective recruitment of leukocytes into the atherosclerotic arterial wall. , 2009, Trends in cardiovascular medicine.

[21]  Bo Li,et al.  Fucoidan: Structure and Bioactivity , 2008, Molecules.

[22]  M. Biran,et al.  MRI of inducible P‐selectin expression in human activated platelets involved in the early stages of atherosclerosis , 2011, NMR in biomedicine.

[23]  Jean-Baptiste Michel,et al.  Intraplaque haemorrhages as the trigger of plaque vulnerability , 2011, European heart journal.

[24]  D Revel,et al.  Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI. , 1993, Magnetic resonance imaging.

[25]  Brian K Rutt,et al.  Imaging single mammalian cells with a 1.5 T clinical MRI scanner , 2003, Magnetic resonance in medicine.

[26]  Jean-Baptiste Michel,et al.  MR imaging of iron phagocytosis in intraluminal thrombi of abdominal aortic aneurysms in humans. , 2010, Radiology.

[27]  Zahi A Fayad,et al.  Chronic Thrombus Detection With In Vivo Magnetic Resonance Imaging and a Fibrin-Targeted Contrast Agent , 2005, Circulation.

[28]  P. Merlet,et al.  99mTc-Annexin-V Functional Imaging of Luminal Thrombus Activity in Abdominal Aortic Aneurysms , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[29]  René M. Botnar,et al.  Molecular Magnetic Resonance Imaging of Atrial Clots in a Swine Model , 2005, Circulation.

[30]  G. Pasterkamp,et al.  Targeting adhesion molecules in cardiovascular disorders. , 2008, Cardiovascular & hematological disorders drug targets.

[31]  F. Chaubet,et al.  Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets. , 2009, Biochimica et biophysica acta.

[32]  Jean-Baptiste Michel,et al.  Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution. , 2006, The American journal of pathology.

[33]  B. Furie,et al.  Role of P-selectin and PSGL-1 in coagulation and thrombosis , 2004, Thrombosis and Haemostasis.

[34]  C. Glüer,et al.  Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging , 2010, International journal of molecular sciences.

[35]  J. Freedman,et al.  Platelets and innate immunity , 2010, Cellular and Molecular Life Sciences.

[36]  C. Goergen,et al.  Molecular Imaging of Experimental Abdominal Aortic Aneurysms , 2013, TheScientificWorldJournal.

[37]  J. Michel,et al.  Role of leukocyte elastase in preventing cellular re-colonization of the mural thrombus. , 2004, The American journal of pathology.

[38]  Chun Yuan,et al.  Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study , 2005, Circulation.

[39]  J. Debatin,et al.  Magnetic Resonance Imaging of Atherosclerotic Plaque With Ultrasmall Superparamagnetic Particles of Iron Oxide in Hyperlipidemic Rabbits , 2001, Circulation.

[40]  Philippe Robert,et al.  Recent advances in iron oxide nanocrystal technology for medical imaging. , 2006, Advanced drug delivery reviews.

[41]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[42]  A. Varki,et al.  Selectin ligands. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. Neubauer,et al.  Magnetic Resonance Imaging of Endothelial Adhesion Molecules in Mouse Atherosclerosis Using Dual-Targeted Microparticles of Iron Oxide , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[44]  J. Alsac,et al.  Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation , 2011, The Journal of Nuclear Medicine.

[45]  J. Deux,et al.  Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation. , 2005, Radiology.

[46]  J. Michel,et al.  Elastase-induced experimental aneurysms in rats. , 1990, Circulation.

[47]  J. Michel,et al.  Low-Molecular-Weight Fucoidan Promotes Therapeutic Revascularization in a Rat Model of Critical Hindlimb Ischemia , 2003, Journal of Pharmacology and Experimental Therapeutics.