Personalized diagnosis and treatment with allogenic or autologous cells are becoming a reality in the field of medicine (1, 2). Cytotoxic or engineered T cells are under clinical trial for the treatment of hematopoietic or other malignant diseases (1). Contrast agent-tagged macrophages are used as cellular probes to image the early inflammatory processes in macrophage-rich conditions such as inflammation, atherosclerosis, and acute cardiac graft rejection (2). The roles of stem cells are under intensive investigation in the therapeutic and regenerative medicine such as regenerating cardiomyocytes, neurons, bone, and cartilage (3). Genetically modified cells are used to treat genetic disorders (4). With the promising results from these studies, a critical issue is how to monitor the temporal and spatial migration and the homing of these cells, as well as the engraftment efficiency and functional capability of the transplanted cells (5, 6). Histopathological techniques have only been used to obtain information on the fate of implanted cells at the time of animal euthanization or biopsy or surgery. To track the real-time changes of cell location, viability, and functional status, cell imaging techniques have been introduced during the last few years. Cells of interest are labeled with reporter genes, fluorescent dyes, or other contrast agents that transform the tagged cells into cellular probes or imaging agents (5-7). The ability to monitor superparamagnetic iron oxide particles (SPIO) by magnetic resonance imaging (MRI) has been utilized in animal models as well as in a few clinical settings to investigate the fate of labeled cells (5-9). The advantages of using MRI for cell tracking include the high spatial resolution with high anatomic background contrast, the lack of exposure to ionizing radiation, and the ability to follow the cells for months. SPIO particles provide a strong change in signal per unit of metal, in particular on 2- and 2*-weight images. In addition, cell labeling with SPIO nanoparticles is generally nontoxic and does not affect the cell proliferation and differentiation capacity, although a few studies have reported that the stem cells labeled with SPIO lose part of their differentiation capacity in a SPIO concentration–dependent manner (8, 9). An important limitation of MRI is the fact that MRI signals cannot indicate whether cells are dead or alive. It is also unknown whether the MRI signal comes from targeted or labeled cells or from macrophages. Basically, SPIO particles are used to label the target cells by systemic application or by injecting into the tissue area of interest to monitor target cell migration after phagocytosis. SPIO are more frequently used to label the cells by incorporating into the cells directly. Furthermore, SPIO are usually encapsulated by organic polymers to increase their stability and bio-compatibility, and allow the chemical modification of their surfaces. The fact is that the uptake of different particles varies largely between different cell types (5, 6). Mesenchymal stem cells (MSCs) represent a heterogeneous subset of pluripotent stromal cells that can be isolated from different adult tissues including adipose tissue, liver, muscle, amniotic fluid, placenta, umbilical cord blood, and dental pulp, although the bone marrow remains the principal source for most preclinical and clinical studies (3, 10, 11). Although MSCs account for only 0.01–0.001% of the total nucleated cells within isolated bone marrow aspirates, they can easily be isolated and expanded through as many as 40 population doublings in ~8–10 weeks of culture (12). These cells exhibit the potential to differentiate into cells of diverse lineages, such as adipocytes, chondrocytes, osteocytes, myoblasts, cardiomyocytes, neurons, and astrocytes. In addition, MSCs possess remarkable immunosuppressive properties, and they have been shown to be effective against tumor cell growth (13, 14). Yoon et al. generated multimodal, rhodamine B isothiocyanate (RITC)-labeled, silica-coated magnetic nanoparticles (MNPs@SiO(RITC)) and Park et al. labeled the MSCs with the nanoparticles and successfully tracked the labeled cells transplanted into the subcutaneous tissue and liver of the mice (7, 15). Their results indicate that MNPs@SiO(RITC) are biocompatible and useful for human MSC labeling and cell tracking with multimodality imaging.