Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: a comparison.
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.
Sun
Rui
R
Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg.
Dittrich
Julia
J
Le-Huu
Martin
M
Mueller
Margareta M
MM
Bedke
Jens
J
Kartenbeck
Juergen
J
Lehmann
Wolf D
WD
Krueger
Ralf
R
Bock
Michael
M
Huss
Ralf
R
Seliger
Christian
C
Gröne
Herrmann-Josef
HJ
Misselwitz
Bernd
B
Semmler
Wolfhard
W
Kiessling
Fabian
F
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
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide