Delivery of fluorescent probes using iron oxide particles as carriers enables in-vivo labeling of migrating neural precursors for magnetic resonance imaging and optical imaging

Iron oxide particles are important contrast agents for magnetic resonance imaging (MRI). In particular, there is rapid growth in their use for experimental cell tracking studies (for recent reviews see Frank ¹ and Bulte and Kraitchman²). Most cell tracking studies by MRI involve labeling cells in culture with an iron oxide contrast agent and transplanting these labeled cells into an animal model.^{3, 4, 5} Recently direct, in-vivo labeling of macrophages⁶ and migrating neural progenitors⁷ have been demonstrated. The advantage of iron oxide particles as contrast agents is their ability to disrupt the homogeneous magnetic field of nearby water molecules, thus producing a hypointense signal on T2 or $\mathrm{T}{2}^{*}$ weighted MRI. A challenge to producing significant contrast is that there must be efficient loading of iron into a cell to be able to visualize it with MRI.⁸ Micron-sized particles of iron oxide (MPIOs) have proven useful for labeling cells for MRI both in vitro and in vivo because they contain high iron oxide content, up to $10\mathrm{pg}$ of iron per particle, as compared to 0.5 attograms/particle for commonly used dextran-loaded iron oxide particles. MPIOs are readily endocytosed by many cell types and do not affect their viability or function.^{9, 10, 11} Indeed, iron labeling of cells with MPIOs is so efficient that recent reports have demonstrated that single cells can be localized with MRI in vivo.^{10, 11, 12} Thus, MPIO labeled cells can provide MRI contrast to map cell location, within the overall anatomy of the tissue.