Cellular Magnetic Resonance Imaging Using Superparamagnetic Anionic Iron Oxide Nanoparticles: Applications to In Vivo Trafficking of Lymphocytes and Cell-Based Anticancer Therapy

: In current cancer research, the application of cytotoxic T lymphocytes with specificity to tumor antigens is regarded as a real therapeutic hope. The objective of imaging is to provide a follow-up of these killer cells in real time, in order to gain a better understanding of the mechanisms and action modes of lymphocytes on the tumor. Magnetic resonance imaging (MRI) has the advantage of the innocuousness of the applied magnetic field. Moreover, it has an exceptional spatial resolution allowing the visualization of anatomical areas without in-depth limitations. These features make MRI particularly adapted for cellular imaging. The use of " (ultrasmall) superparamagnetic iron oxide " particles [(U) SPIO] offers the adequate sensitivity required for cellular imaging. To promote a sufficient capture of these particles in nonphagocytic cells and make the cell of interest " detectable " by MRI after its injection, an important challenge in cellular imaging is to develop improved cell-labeling techniques. Superparamagnetic anionic nanoparticles (iron oxides of 10-nm diameter) are adsorbed in a nonspecific way on the membrane of the majority of cells, allowing their spontaneous internalization in intracellular vesicles. This pathway of cellular labeling confers a particular status to these nanoparticles as MRI contrast agents; the cells labeled in this manner possess magnetic and contrast properties that allow their in vivo detection and follow-up by MRI. This chapter describes the synthesis, the potential use, and the features of cellular labeling with these types of anionic nanoparticles. We also focus on the MRI contrast properties of the labeled cells, as well as on the feasibility of in vivo detection of immunizing circulating cells by MRI, with direct implications in cell-based anticancer therapy using lymphocytes.