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Published online before print March 4, 2005, 10.1148/radiol.2351040094
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(Radiology 2005;235:155-161.)
© RSNA, 2005


Molecular Imaging

Cell Tagging with Clinically Approved Iron Oxides: Feasibility and Effect of Lipofection, Particle Size, and Surface Coating on Labeling Efficiency1

Lars Matuszewski, MD, Thorsten Persigehl, MD, Alexander Wall, MD, Wolfram Schwindt, MD, Bernd Tombach, MD, Manfred Fobker, MD, Christopher Poremba, MD, Wolfgang Ebert, PhD, Walter Heindel, MD and Christoph Bremer, MD

1 From the Departments of Clinical Radiology (L.M., T.P., A.W., W.S., B.T., W.H., C.B.) and Clinical Chemistry (M.F.), University Hospital Muenster, Albert-Schweitzer-Str 33, D-48129 Muenster, Germany; Department of Pathology, University of Duesseldorf, Duesseldorf, Germany (C.P.); Schering, Berlin, Germany (W.E.); and Interdisciplinary Center for Clinical Research, University of Muenster, Muenster, Germany (C.B.). Received January 26, 2004; revision requested March 11; revision received May 24; accepted June 28. Address correspondence to C.B. (e-mail: bremerc@uni-muenster.de).

PURPOSE: To evaluate the effect of lipofection, particle size, and surface coating on labeling efficiency of mammalian cells with superparamagnetic iron oxides (SPIOs).

MATERIALS AND METHODS: Institutional Review Board approval was not required. Different human cell lines (lung and breast cancer, fibrosarcoma, leukocytes) were tagged by using carboxydextran-coated SPIOs of various hydrodynamic diameters (17–65 nm) and a dextran-coated iron oxide (150 nm). Cells were incubated with increasing concentrations of iron (0.01–1.00 mg of iron [Fe] per milliliter), including or excluding a transfection medium (TM). Cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic emission spectroscopy. Cell visibility was assessed with gradient- and spin-echo magnetic resonance (MR) imaging. Effects of iron concentration in the medium and of lipofection on cellular SPIO uptake were analyzed with analysis of variance and two-tailed Student t test, respectively.

RESULTS: Iron oxide uptake increased in a dose-dependent manner with higher iron concentrations in the medium. The TM significantly increased the iron load of cells (up to 2.6-fold, P < .05). For carboxydextran-coated SPIOs, larger particle size resulted in improved cellular uptake (65 nm, 4.37 µg ± 0.08 Fe per 100 000 cells; 17 nm, 2.14 µg ± 0.06 Fe per 100 000 cells; P < .05). Despite larger particle size, dextran-coated iron oxides did not differ from large carboxydextran-coated particles (150 nm, 3.81 µg ± 0.46 Fe per 100 000 cells; 65 nm, 4.37 µg ± 0.08 Fe per 100 000 cells; P > .05). As few as 10 000 cells could be detected with clinically available MR techniques by using this approach.

CONCLUSION: Lipofection-based cell tagging is a simple method for efficient cell labeling with clinically approved iron oxide–based contrast agents. Large particle size and carboxydextran coating are preferable for cell tagging with endocytosis- and lipofection-based methods.

© RSNA, 2005




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