Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization

Authors Wagner S, Schnorr J, Ludwig A, Stangl V, Ebert M, Hamm B, Taupitz M

Received 1 October 2012

Accepted for publication 2 December 2012

Published 20 February 2013 Volume 2013:8(1) Pages 767—779

DOI https://doi.org/10.2147/IJN.S38702

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Susanne Wagner,1 Jörg Schnorr,1 Antje Ludwig,2 Verena Stangl,2 Monika Ebert,1 Bernd Hamm,1 Matthias Taupitz1

1Department of Radiology, Section of Experimental Radiology, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, and Campus Benjamin Franklin, Berlin, Germany; 2Department of Cardiology, Section of Experimental Cardiology, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany

Objective: To evaluate the suitability of citrate-coated very small superparamagnetic iron oxide particles (VSOP) as a contrast agent for identifying inflammation in atherosclerotic lesions using magnetic resonance imaging (MRI).
Methods and results: VSOP, which have already been evaluated as a blood pool contrast agent for MR angiography in human clinical trials, were investigated in Watanabe heritable hyperlipidemic rabbits to determine to what extent their accumulation in atherosclerotic lesions is a function of macrophage density and other characteristics of progressive atherosclerotic plaques. In advanced atherosclerotic lesions, a significant MRI signal loss was found within 1 hour after intravenous administration of VSOP at the intended clinical dose of 0.05 mmol Fe/kg. Histological examinations confirmed correlations between the loss of MRI signal in the vessel wall and the presence of Prussian blue-stained iron colocalized with macrophages in the plaque cap, but surprisingly also with calcifying microvesicles at the intimomedial interface. Critical electrolyte magnesium chloride concentration in combination with Alcian blue stain indicates that highly sulfated glycosaminoglycans are a major constituent of these calcifying microvesicles, which may serve as the key molecules for binding VSOP due to their highly complexing properties.
Conclusion: Calcifying microvesicles and macrophages are the targets for intravenously injected VSOP in atherosclerotic plaques, suggesting that VSOP-enhanced MRI may render clinically relevant information on the composition and inflammatory activity of progressive atherosclerotic lesions at risk of destabilization.

Keywords: atherosclerosis, inflammation, magnetic resonance imaging, iron oxide nanoparticles, glycosaminoglycans, calcifying microvesicles

A Letter to the Editor has been received and published for this article.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Mesenchymal stromal cell labeling by new uncoated superparamagnetic maghemite nanoparticles in comparison with commercial Resovist – an initial in vitro study

Skopalik J, Polakova K, Havrdova M, Justan I, Magro M, Milde D, Knopfova L, Smarda J, Polakova H, Gabrielova E, Vianello F, Michalek J, Zboril R

International Journal of Nanomedicine 2014, 9:5355-5372

Published Date: 20 November 2014

Comparison of the clinical features and outcomes in two age-groups of elderly patients with atrial fibrillation

Shao XH, Yang YM, Zhu J, Zhang H, Liu Y, Gao X, Yu LT, Liu LS, Zhao L, Yu PF, Zhang H, He Q, Gu XD

Clinical Interventions in Aging 2014, 9:1335-1342

Published Date: 12 August 2014

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

Vandooren J, Berghmans N, Dillen C, Van Aelst I, Ronsse I, Israel LL, Rosenberger I, Kreuter J, Lellouche JP, Michaeli S, Locatelli E, Comes Franchini M, Aiertza MK, Sánchez-Abella L, Loinaz I, Edwards DR, Shenkman L, Opdenakker G

International Journal of Nanomedicine 2013, 8:4745-4756

Published Date: 13 December 2013

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Bian X, Liang S, John J, Hsiao CH, Wei X, Liang D, Xie H

International Journal of Nanomedicine 2013, 8:4521-4531

Published Date: 21 November 2013

Dextran-b-poly(L-histidine) copolymer nanoparticles for pH-responsive drug delivery to tumor cells

Hwang JH, Choi CW, Kim HW, Kim DH, Kwak TW, Lee HM, Kim CH, Chung CW, Jeong YI, Kang DH

International Journal of Nanomedicine 2013, 8:3197-3207

Published Date: 21 August 2013

Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Liu CC, Zhu Q, Wu WH, Xu XL, Wang XY, Gao S, Liu KH

International Journal of Nanomedicine 2012, 7:5339-5350

Published Date: 8 October 2012

Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid

Nagehan Saltan, H Mehtap Kutlu, Deniz Hür

International Journal of Nanomedicine 2011, 6:477-484

Published Date: 28 February 2011