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 T 2 (*)-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.

Background-We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods and Results-Adult farm pigs (nϭ5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16ϫ10 Key Words: magnetic resonance imaging Ⅲ myocardial infarction Ⅲ cells Ⅲ contrast media B ecause of the limited regenerative capacity of the heart muscle, mesenchymal stem cells (MSCs), found in bone marrow, may have enormous therapeutic potential for limiting infarct size and restoring cardiac function after irreversible ischemic injury. Most techniques for the study of stem cell transplantation in animal models require histological analysis to determine the fate and migration of cells. [1][2][3][4][5] Thus, the number and location of MSCs delivered using intramyocardial delivery techniques can only be estimated postmortem. The recent ability to label MSCs 6 with magnetic resonance imaging (MRI)-visible contrast agents should enable serial tracking and quantification of MSC transplantation noninvasively with high spatial resolution. Thus, the purpose of this study was to determine whether magnetically labeled MSCs injected intramyocardially could be detected and tracked noninvasively by MRI in a swine model of myocardial infarction. Methods Animal ModelAnimal studies were approved by the Institutional Animal Care and Use Committee. The evening before creation of a myocardial infarction (MI), 5 farm pigs (25 to 35 kg; Archer Farms, Belcamp, Md) received aspirin (325 mg) and diltiazem (180 mg sustained release) orally. Animals were sedated with acepromazine, ketamine, and atropine; induced with thiopental; and then intubated and mechanically ventilated with oxygen and isoflurane. To create MI, cardiac catheterization was performed via a 9F carotid sheath, and a 2.0 or 2.5ϫ20-mm coronary angioplasty balloon (Cordis, Inc) was inflated in the left anterior descending (LAD) artery beyond the first diagonal branch to occlude LAD flow for 60 minutes, followed by reperfusion. After allowing for stabilization, allogeneic MSCs were given by intramyocardial injection using a deflectable guiding catheter and a helical needle (Biocardia, Inc). In 4 animals, MRMSCs were injected; 1 control animal received nonlabeled MSCs. Magnetically Labeled MSCsSwine mesenchymal stem cells were isolated and cultured as previously described. 7 The MSCs were culture-expanded 2 or 3 passages in vitro, yielding up to 400 million cells, which were frozen and thawed for use. In two studies, before freezing, the MSCs were fluorescently labeled with DiI (1,1Ј-dioctadecyl-3,3,3Ј3Ј-testramethylindocarbocyanine perchlorate) and DAPI (4Ј,6-Diamidino-2-phenylindole), which preferentially stain cells membranes and nuclei, respectively.The swine MSCs were magnetically labeled by incubation with ferumoxides injectable solution (25 g Fe/mL, Feridex, Berlex Laboratories) in culture medium for 24 to 48 hours with 375 ng/mL poly-L-lysine (PLL; average MWϭ275 kDa) added ...

Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions— Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.