title: Functionalized magnetic resonance contrast agent selectively binds to glycoprotein IIb/IIIa on activated human platelets under flow conditions and is detectable at clinically relevant field strengths.
abstract: Recent progress in molecular magnetic resonance imaging (MRI) provides the opportunity to image cells and cellular receptors using microparticles of iron oxide (MPIOs). However, imaging targets on vessel walls remains challenging owing to the quantity of contrast agents delivered to areas of interest under shear stress conditions. We evaluated ex vivo binding characteristics of a functional MRI contrast agent to ligand-induced binding sites (LIBSs) on activated glycoprotein IIb/IIIa receptors of human platelets, which were lining rupture-prone atherosclerotic plaques and could therefore facilitate detection of platelet-mediated pathology in atherothrombotic disease. MPIOs were conjugated to anti-LIBS single-chain antibodies (LIBS-MPIO) or control antibodies (control MPIO). Ex vivo binding to human platelet-rich clots in a dose-dependent manner was confirmed on a 3 T clinical MRI scanner and by histology (p < .05 for LIBS-MPIO vs control MPIO). By using a flow chamber setup, significant binding of LIBS-MPIO to a platelet matrix was observed under venous and arterial flow conditions, but not for control MPIO (p < .001). A newly generated MRI contrast agent detects activated human platelets at clinically relevant magnetic field strengths and binds to platelets under venous and arterial flow conditions, conveying high payloads of contrast to specific molecular targets. This may provide the opportunity to identify vulnerable, rupture-prone atherosclerotic plaques via noninvasive MRI.
authors.affiliation: Department of Cardiology and Angiology, University Hospital of Freiburg, Freiburg, Germany. constantin.vonzurmuehlen@uniklinik-freiburg.de
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Muhlen
authors.forename: Dominik
authors.initials: D
authors.lastname: von Elverfeldt
authors.forename: Robin Paul
authors.initials: RP
authors.lastname: Choudhury
authors.forename: Janine
authors.initials: J
authors.lastname: Ender
authors.forename: Ingo
authors.initials: I
authors.lastname: Ahrens
authors.forename: Meike
authors.initials: M
authors.lastname: Schwarz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hennig
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000906:Antibodies / Q000378:metabolism; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000378:metabolism*; D003287:Contrast Media / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010316:Particle Size; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*
chemical_list: D000906:Antibodies; D003287:Contrast Media; D005290:Ferric Compounds; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C000499:ferric oxide