Bulte JW, Kraitchman DLIron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484-499

Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
NMR in Biomedicine (Impact Factor: 3.04). 11/2004; 17(7):484-99. DOI: 10.1002/nbm.924
Source: PubMed


Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2(*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the 'proof-of-principle' type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors.

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Available from: Jeff Bulte, Jul 01, 2015
    • "Macrophages have a crucial role in the initiation and modulation of inflammatory processes in response to a variety of stimulus such as foreign particles, bacteria, oxidative stress and cytokines (Duffield, 2003). While NP association with macrophages may be desirable for applications where targeting of pathological inflammated tissue is required (Bulte and Kraitchman, 2004), for many other nanomedicine applications it is not. Therefore, the induction of a pro-inflammatory response by macrophages, namely cytokine production, can be classified as an unwanted reaction for nanomedicines since their constant overproduction is associated directly or indirectly to the pathogenesis of several autoimmune diseases, and their levels are commonly elevated in patients with cancer, cardiovascular and inflammatory diseases (Hansson, 2009; Medzhitov, 2008). "
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    • "c o m / l o c a t e / c e j superparamagnetic behavior) [10]. Moreover, the magnetic core is biodegradable and iron ions are reused by cells using normal biochemical pathways for Fe metabolism [11]. Biocompatible surface coatings with hydrophilic polymers such as poly (ethylene glycol), dextran or chitosan were carried out to improve the colloidal stability and to prolong circulation kinetics of magnetic nanoplatforms [12] [13] [14]. "
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    • "As an example of their clinical use, SPIO nanoparticles have been used to track, using MRI, the homing of injected mesenchymal stem cells to the central nervous system (CNS) of individuals with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) (Karussis et al., 2010). This approach is particularly valuable because SPIO nanoparticle labeling does not affect the differentiation capacity (Nejadnik et al., 2012a; Wang et al., 2011), viability or function (Richards et al., 2012) of transplanted stem cells, except for chondrogenesis by mesenchymal stem cells, where it interferes with forming the extracellular matrix of cartilage (Bulte et al., 2004; Kostura et al., 2004). "
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