Superparamagnetic iron-oxide particles (SPIO) are used in different ways as contrast agents for magnetic resonance imaging (MRI): Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite), different coatings (none, dextran, carboxydextran, polystyrene) and different hydrodynamic diameters (20–850 nm) for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC), which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.

The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1–92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature.Electronic supplementary materialThe online version of this article (doi:10.1007/s10585-011-9403-y) contains supplementary material, which is available to authorized users.

In this study a liposome cell labeling system was developed for non-target-specific labeling of glioma cells with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging (MRI). A high non-target-specific uptake is ideal for in vitro labeling of cells and subsequently for cell tracking and visualization of phagocytic cells in vivo. The preparation of iron oxide-loaded liposomes was optimized and the biological properties of the liposomes were investigated. Cytotoxicity and cell viability were examined and showed limited cytotoxic effects. Non-target-specific labeling of glioma cells in vitro for subsequent specific labeling of molecules for MR imaging was tested by T2*-weighted MRI at 3T. The glioma cells showed a strong initial uptake of the iron oxide liposomes and the uptake was not saturable within 24 h exposure. The uptake of liposomes was superior to non-coated magnetite nanoparticles. Using PEG-ylated liposomes, the non-specific uptake could be decreased fundamentally (86% lower) in comparison to conventional liposomes. Furthermore, the ability of liposomes as contrast agents for MR imaging was investigated. Cells labeled with iron oxide nanoparticles by treatment with liposomes showed a negative contrast in MRI and consequently successful cellular labeling. Thus, iron oxide-loaded liposomes are well suited for non-target-specific cell labeling for MR imaging.