Moreover, they have a high relaxation level and therefore can exhibit an imaging effect (contrast) even at a lower concentration. Furthermore, the above-mentioned composite particles are accumulated in tumors due to the enhanced permeability and retention effect (EPR effect). The composite particles according to the present invention to which high molecular weight graft chains were bound at a very high density by living radical polymerization have high dispersion stability and tend not to be phagocytized by reticuloendothelial cells and therefore tend not to be accumulated in tissues such as a liver and a spleen. The present invention is an MRI contrast agent containing composite particles, wherein the composite particles are those with polymer graft chains bound to surfaces of microparticles at a very high density sufficient to allow steric repulsion to occur between the graft chains, the microparticles are inorganic microparticles that exhibit superparamagnetism, and the polymer graft chains have a number average molecular weight (Mn) of at least 30,000. Therefore, the present inventors aim to provide an MRI contrast agent that has high dispersion stability and improved functions and that tends not to be phagocytized by macrophages. However, such conventional preparations have low dispersion stability and tend to be phagocytized by macrophages, which have been problems. 2009-519316ĭISCLOSURE OF INVENTION Problem to be Solved by the Invention Patent Document 2: Japanese Unexamined Patent Application Publication No.Thus, the conventional gadolinium preparations and iron preparations have problems in pharmacokinetics when being administered to biological bodies.Īs an example of the methods in which the pharmacokinetics after administration to a biological body has been improved, a method of coating the surfaces of inorganic core nanoparticles with polymers through, for example, silane groups has been proposed (for example, Patent Document 2). On the other hand, although iron preparations with a high stability in blood and low liver accumulation also have been clinically developed (for example, Patent Document 1), they are shown to be phagocytized mainly by macrophages and to have a high accumulation in lymph nodes and therefore are no different in terms of a tendency to be taken into the reticuloendothelial system. Therefore, as MRI contrast agents, they can be used only for negative imaging of liver tumors. Generally, however, conventional iron preparations are taken into normal liver tissue in just a matter of minutes after intravenous administration but are not taken into tumor regions in the liver at all. For the MRI contrast agents, generally, magnetic materials that affect nuclear magnetic resonance are used and, for example, gadolinium preparations and iron preparations are commercially available.Īs compared to the gadolinium preparations, the iron preparations have the advantages of being excellent in biological safety and producing excellent imaging effects at low doses. The contrast agents are pharmaceutical agents for use in examinations to enhance the image contrast between a normal tissue and a target tissue in diagnosis and are usually used by intravenous injection. In the MRI method (the magnetic resonance imaging method) that is one of the in vivo diagnostic imaging methods, contrast agents are often used in order to image specific tissues more clearly. The present invention relates to an MRI contrast agent containing composite particles.
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