1. Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
- Author
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Alexander, Maier, Moritz, Braig, Katharina, Jakob, Thomas, Bienert, Michaela, Schäper, Annette, Merkle, Carolin, Wadle, Marius, Menza, Irene, Neudorfer, István, Bojti, Peter, Stachon, Daniel, Duerschmied, Ingo, Hilgendorf, Timo, Heidt, Christoph, Bode, Karlheinz, Peter, Karin, Klingel, Dominik, von Elverfeldt, and Constantin, von Zur Mühlen
- Subjects
Blood Platelets ,Male ,Platelet Membrane Glycoprotein IIb ,Mice, Inbred BALB C ,Binding Sites ,lcsh:R ,Integrin beta3 ,Cardiology ,Contrast Media ,lcsh:Medicine ,Platelet Activation ,Magnetic Resonance Imaging ,Article ,Disease Models, Animal ,Mice ,Myocarditis ,Early Diagnosis ,Medical research ,Animals ,Humans ,lcsh:Q ,Cardiomyopathies ,lcsh:Science - Abstract
MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund’s adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.
- Published
- 2020
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