Magnetic resonance imaging of experimental atherosclerotic plaque: Comparison of two ultrasmall superparamagnetic particles of iron oxide

Abstract

Purpose: To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. Materials and Methods:Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 mol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric WilcoxonMann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed.Results: MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P Ͻ 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. Conclusion:Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.

Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis

“…TNP used in this study was administered at 1.5 mg Fe/kg body weight, well below the dose currently in clinical trials for oncology (2.6 mg Fe/kg) 24 and the dose used experimentally for imaging of atherosclerosis in rabbits (14 to 56 mg Fe/kg). 3,4 We anticipate that the detection threshold could easily be improved by several orders of magnitude with further chemical optimization aiming at higher specific activity of the nanoparticle, as well as with the higher sensitivity of the next generation of PET imaging systems.…”

“…For example, magnetic resonance imaging (MRI) studies have used nanoparticles to report areas of inflamed lesions in animals [2][3][4][5][6] and in carotid artery plaques in patients. 7,8 Although MRI provides unparalleled versatility and soft tissue contrast, 9 direct visualization of abnormalities often requires relatively large amounts of nanoparticles (2 to 20 mg Fe/kg).…”

Potential of Magnetic Resonance Plaque Imaging Using Superparamagnetic Particles of Iron Oxide for the Detection of Carotid Plaque

“…1,2,5,19) Atherosclerotic plaque has recently been imaged in hyperlipidemic rabbits using ultrasmall superparamagnetic particles of iron oxide (SPIO) for functional MR imaging. 4,9,13,14) More recently, the ultra-small SPIO agent Sinerem  (Guerbet, Paris, France) has been used for the evaluation of human carotid plaque. 6,15,17,18) Ultra-small SPIO consists of iron oxide nanoparticles stabilized with low molecular weight dextran with a diameter of 30 nm and has a long plasma half-life.…”

Iron Oxide Particles for Atheroma Imaging

“…8,9 The use of a USPIO agent, Sinerem (Guerbet; Ferumoxtran-10), has allowed the direct visualization of macrophage infiltration of carotid atheroma in vivo. [5][6][7][8][9][10][11][12] The hypothesis that Sinerem may be useful in the assessment of inflammatory activity in atherosclerotic plaque is strongly supported by the endothelial dysfunction theory. 13 Dysfunctional endothelium initiates and sustains an inflammatory reaction within the arterial wall and allows for the accumulation of plasma components, such as low-density lipoproteins (LDL), in the subendothelial space.…”