MOLECULAR IMAGING (G STRIJKERS, SECTION EDITOR) The Use of Superparamagnetic Iron Oxide Nanoparticles to Assess Cardiac Inflammation Colin G. Stirrat & David E. Newby & Jennifer M. J. Robson & Maurits A. Jansen # Springer Science+Business Media New York 2014 Abstract Superparamagnetic iron oxide-based contrast agents enhance and complement in vivo magnetic resonance imaging (MRI) by shortening T2 and T2* relaxation times. They are able to highlight areas of cellular inflammation, being detected and engulfed by cells of the reticuloendothelial system, and can be targeted to specific cellular processes or subtypes using antibody or ligand labeling. These agents have been used preclinically for the assessment of cardiac trans- plant rejection, cardiomyocyte apoptosis, myocardial infarc- tion, myocarditis, and stem and endothelial cell imaging, with clinical applications now emerging. We here review recent studies using iron oxide particles to image cardiac inflamma- tion, and highlight the potential of these agents for future clinical and research applications. Keywords Cardiac . MRI . Iron oxide nanoparticles . Inflammation . Molecular imaging Introduction Overview of Iron Oxide Nanoparticles In many inflammatory diseases of the myocardium, endomyocardial biopsy is the ‘gold standard’ diagnostic in- vestigation. However, this does carry the potential for life- threatening complications [1], and false negative or inconclu- sive results are not uncommon due to the focal nature and spatial heterogeneity of the underlying inflammatory disease process. Development of a reliable noninvasive imaging tech- nique capable of detecting myocardial inflammation would be extremely beneficial and a major advance. This could provide a diagnosis in patients displaying early signs suggestive of myocardial inflammation or with subclinical disease, creating an opportunity to prevent the disease process from become established or limit its progression. Furthermore, this could provide a surrogate measure of treatment response and facil- itate serial disease monitoring. Iron oxide nanoparticles can be used for molecular and cellular imaging [2], and thereby enhance the sensitivity of magnetic resonance imaging (MRI) to detect and characterize various pathologic processes [3]. They rely on the principle that accumulation of superparamagnetic iron oxide particles within tissues causes local magnetic field inhomogeneities that shorten T2 and T2* relaxation times. They generally consist of an iron oxide core surrounded by a carbohydrate or polymer coat that prevents aggregation and oxidation of the iron, and provides a surface for conjugation of drug molecules and targeting ligands. A range of particles exists and they vary in size and coating. These 2 properties of iron nanoparticles are the key determinants of their biodistribution, magnetic behavior and, thus, the potential applications of the particle [4, 5]. Iron oxide particles can be categorized according to their size (Table 1): nano-sized very small (VSPIO, <20 nm in diameter), ultrasmall (USPIO, 20–50 nm in diameter) and small (SPIO, 60–250 nm in diameter) superparamagnetic par- ticles of iron oxide, and micrometer-sized (MPIO, 1–8 μm in diameter) particles of iron oxide. The ‘superparamagnetic’ particles become magnetic within a strong external magnetic field such as exists within an MRI scanner, but do not retain their magnetism once removed from the field. Iron oxide particles were initially used as contrast agents for imaging of the gastrointestinal tract [6], the Kupffer cells of the liver and spleen [7], and lymph nodes [8], as well as a This article is part of the Topical Collection on Molecular Imaging C. G. Stirrat (*) : D. E. Newby : J. M. J. Robson : M. A. Jansen British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Room SU 305 Chancellor’ s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK e-mail: colin.stirrat@ed.ac.uk Curr Cardiovasc Imaging Rep (2014) 7:9263 DOI 10.1007/s12410-014-9263-3