Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.

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Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bisoleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPAphosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion-and particle-based r 1 relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM) -1 and 2.48 ؋ 10 6 (s*mM) -1 , respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% ؎ 5% higher change in R 1 values at 1.5 T (⌬R 1 ‫؍‬ 0.77 ؎ 0.02 1/s) relative to Gd-DTPA-BOA (⌬R 1 ‫؍‬ 0.45 ؎ 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack. The acute formation of thrombus on ruptured atherosclerotic plaques is well recognized as the source of unstable angina, myocardial infarction, transient ischemic attacks, and stroke (1). Although myriad medical advances in the detection and treatment of advanced carotid and coronary artery disease have emerged, early detection of the most common source of thromboembolism-rupturing atherosclerotic plaques in arteries with modest 40-60% stenosis (2)-remains diagnostically elusive with the use of routine angiography or duplex ultrasound techniques.A variety of approaches have been proposed to improve detection of vulnerable plaques, including intravascular ultrasound elastography (3), radionuclide imaging (4), and thermography (5). Magnetic resonance imaging (MRI) also is emerging as a particularly sensitive modality to noninvasively visualize thromboses within the carotid artery (6). However, the proximate cause of heart attacks and strokes-rupture of the vulnerable plaque-cannot be reliably detected with any nondestructive imaging modality.Recent studies reveal that vulnerable plaque rupture and microthrombus formation precedes acute myocardial infarction by days to months (7), providing a window of opportunity to intercede and prevent serious sequelae. Sensitive molecular imaging and detection of microthrombi along the intimal surface of vulnerable plaques will require a high-avidity, target-specific probe with robust signal amplification compatible with a sensitive, high-resolution imaging modality. Until recently, the signal amplification required to detect and visualize important molecular or cellular moieties present in nano-and picomolar concentrations in vivo was obtainable only with nuclear imaging modalities. However, more recently, molecular imaging with magnetic resonance has shown promise (8,9).A new approach entails the use of a fibrin-specific paramagnetic molecular imaging agent to improve detection and quantification of these...