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Anti-ligand–induced binding sites (LIBS) antibody conjugated to microparticles of iron oxide.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Jun 21 [updated 2010 Sep 03].


Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of nuclear proton spins, the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide (CLIO) and other iron oxide formulations affect T2 primarily and lead to a decreased signal. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd3+) and manganese (Mn2+), accelerate T1 relaxation and lead to increased contrast images. Thrombosis plays a major role in many cardiovascular diseases, such as myocardial infarction, pulmonary embolism (PE), deep venous thrombosis (DVT), atherothrombosis, or cerebral venous thrombosis (2, 3). DVT is a significant cause of PE, which is a potentially life-threatening clinical problem. Thrombosis occurs when platelets deposit in regions of low flow in the deep venous system, followed by an activation process of thrombin, which then converts fibrinogen into fibrin. Platelets become activated and bind to fibrinogen, resulting in platelet aggregation via the platelet integrin GPIIb/IIIa (αIIbβ3, CD61/CD41). The thrombus may become organized or detached from the vessel wall. A single-chain antibody (anti-LIBS 145) has been developed to recognize ligand-induced binding sites (LIBS) of GPIIb/IIIa that become exposed only upon receptor-ligand binding (4). Anti-LIBS 145 single-chain antibody does not bind to circulating platelets. Anti-LIBS 145 single-chain antibody was conjugated to microparticles of iron oxide (MPIOs) to form LIBS-MPIOs for T2-weighted MRI imaging of platelet-containing thrombi (5-8).

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