Atorvastatin and uptake of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) in human monocyte-macrophages: implications for magnetic resonance imaging.
Ferumoxtran-10 is an ultrasmall superparamagnetic iron oxide nanoparticle potentially useful as a contrast material in magnetic resonance imaging for the diagnosis of inflammatory and degenerative disorders associated with high macrophage activity. In clinical trials, it is currently applied to monitor the effect of atorvastatin therapy on macrophage activity in human carotid plaques. A recent study reported the inhibition of iron oxide nanoparticle uptake in macrophages by lovastatin, an effect which could compromise the suitability of Ferumoxtran-10 as an MRI contrast material in patients on statin therapy. Therefore, we examined the effect of atorvastatin on human monocyte-macrophage uptake of Ferumoxtran-10 in vitro using biochemical assays, magnetic resonance imaging and transmission electron microscopy. Our study showed that non-toxic concentrations of atorvastatin did not affect the amount of Ferumoxtran-10 taken up by HMMs. Furthermore, the intracellular distribution of iron oxide nanoparticles and the resulting MRI signal intensities remained unchanged by statin treatment. These results were obtained using atorvastatin concentrations probably vastly exceeding those reached in patient plasma in vivo. Atorvastatin therapy itself is therefore unlikely to affect Ferumoxtran-10 based macrophage detection by MRI, a prerequisite for the use of this contrast material to monitor lesion macrophage burden during lipid-lowering therapy.
Müller
Karin
K
Multi-Imaging Centre, Department of Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. khm20@cam.ac.uk
Skepper
Jeremy N
JN
Tang
Tjun Y
TY
Graves
Martin J
MJ
Patterson
Andrew J
AJ
Corot
Claire
C
Lancelot
Eric
E
Thompson
Paul W
PW
Brown
Andrew P
AP
Gillard
Jonathan H
JH
D000069059:Atorvastatin; D002478:Cells, Cultured; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D052203:Ferrosoferric Oxide; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000494:pharmacology; D007501:Iron / Q000493:pharmacokinetics*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D053758:Nanoparticles / Q000737:chemistry*; D010087:Oxides / Q000493:pharmacokinetics*; D010316:Particle Size; D011758:Pyrroles / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003287:Contrast Media; D003911:Dextrans; D006538:Heptanoic Acids; D058185:Magnetite Nanoparticles; D010087:Oxides; D011758:Pyrroles; C097921:ferumoxtran-10; D000069059:Atorvastatin; D007501:Iron; D006903:Hydroxymethylglutaryl CoA Reductases; D013755:Tetradecanoylphorbol Acetate; D052203:Ferrosoferric Oxide