title: Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison.
abstract: BACKGROUND
  Superparamagnetic iron-oxide particles are used frequently for cellular magnetic resonance imaging and in vivo cell tracking. The purpose of this study was to compare the labeling characteristics and efficiency as well as toxicity of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) for 3 cell lines.
  
  
  METHODS
  Using human fibroblasts, immortalized rat progenitor cells and HEP-G2-hepatoma cells, dose- and time-dependence of SPIO and USPIO uptake were evaluated. The amount of intracellular (U)SPIO was monitored over 2 weeks after incubation by T2-magnetic resonance relaxometry, ICP-mass-spectrometry, and histology. Transmission-electronmicroscopy was used to specify the intracellular localization of the endocytosed iron particles. Cell death-rate and proliferation-index were assessed as indicators of cell-toxicity.
  
  
  RESULTS
  For all cell lines, SPIO showed better uptake than USPIO, which was highest in HEP-G2 cells (110 +/- 2 pg Fe/cell). Cellular iron concentrations in progenitor cells and fibroblasts were 13 +/- 1pg Fe/cell and 7.2 +/- 0.3pg Fe/cell, respectively. For all cell lines T2-relaxation times in cell pellets were below detection threshold (<3 milliseconds) after 5 hours of incubation with SPIO (3.0 micromol Fe/mL growth medium) and continued to be near the detection for the next 6 days. For both particle types and all cell lines cellular iron oxide contents decreased after recultivation and surprisingly were found lower than in unlabeled control cells after 15 days. Viability and proliferation of (U)SPIO-labeled and unlabeled cells were not significantly different.
  
  
  CONCLUSIONS
  The hematopoetic progenitor, mesenchymal fibroblast and epithelial HEP-G2 cell lines accumulated SPIO more efficiently than USPIO indicating SPIO to be better suited for cell labeling. However, the results indicate that there may be an induction of forced cellular iron elimination after incubation with (U)SPIO.
authors: Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg.
authors: Rui
authors: R
authors: Sun
authors: Julia
authors: J
authors: Dittrich
authors: Martin
authors: M
authors: Le-Huu
authors: Margareta M
authors: MM
authors: Mueller
authors: Jens
authors: J
authors: Bedke
authors: Juergen
authors: J
authors: Kartenbeck
authors: Wolf D
authors: WD
authors: Lehmann
authors: Ralf
authors: R
authors: Krueger
authors: Michael
authors: M
authors: Bock
authors: Ralf
authors: R
authors: Huss
authors: Christian
authors: C
authors: Seliger
authors: Herrmann-Josef
authors: HJ
authors: Gröne
authors: Bernd
authors: B
authors: Misselwitz
authors: Wolfhard
authors: W
authors: Semmler
authors: Fabian
authors: F
authors: Kiessling
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003287:Contrast Media / Q000493:pharmacokinetics* / Q000633:toxicity*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D005347:Fibroblasts; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics* / Q000633:toxicity*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000493:pharmacokinetics* / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D013194:Staining and Labeling; D013234:Stem Cells; D014407:Tumor Cells, Cultured
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide