Magnetic resonance imaging contrast of iron oxide nanoparticles developed for hyperthermia is dominated by iron content.
OBJECTIVE
Magnetic iron oxide nanoparticles (MNPs) are used as contrast agents for magnetic resonance imaging (MRI) and hyperthermia for cancer treatment. The relationship between MRI signal intensity and cellular iron concentration for many new formulations, particularly MNPs having magnetic properties designed for heating in hyperthermia, is lacking. In this study, we examine the correlation between MRI T2 relaxation time and iron content in cancer cells loaded with various MNP formulations.


METHODS
Human prostate carcinoma DU-145 cells were loaded with starch-coated bionised nanoferrite (BNF), iron oxide (Nanomag® D-SPIO), Feridex™, and dextran-coated Johns Hopkins University (JHU) particles at a target concentration of 50 pg Fe/cell using poly-D-lysine transfection reagent. T2-weighted MRI of serial dilutions of these labelled cells was performed at 9.4 T and iron content quantification was performed using inductively coupled plasma mass spectrometry (ICP-MS). Clonogenic assay was used to characterise cytotoxicity.


RESULTS
No cytotoxicity was observed at twice the target intracellular iron concentration (∼100 pg Fe/cell). ICP-MS revealed highest iron uptake efficiency with BNF and JHU particles, followed by Feridex and Nanomag-D-SPIO, respectively. Imaging data showed a linear correlation between increased intracellular iron concentration and decreased T2 times, with no apparent correlation among MNP magnetic properties.


CONCLUSIONS
This study demonstrates that for the range of nanoparticle concentrations internalised by cancer cells the signal intensity of T2-weighted MRI correlates closely with absolute iron concentration associated with the cells. This correlation may benefit applications for cell-based cancer imaging and therapy including nanoparticle-mediated drug delivery and hyperthermia.
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore .
Michele
M
Wabler
Wenlian
W
Zhu
Mohammad
M
Hedayati
Anilchandra
A
Attaluri
Haoming
H
Zhou
Jana
J
Mihalic
Alison
A
Geyh
Theodore L
TL
DeWeese
Robert
R
Ivkov
Dmitri
D
Artemov
D003287:Contrast Media; D005290:Ferric Compounds / Q000008:administration & dosage*; D006979:Hyperthermia, Induced; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053768:Metal Nanoparticles
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide