Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-f
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BioMed Central
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Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS Emily A Waters1,2, Junjie Chen1, John S Allen1, Huiying Zhang1, Gregory M Lanza1 and Samuel A Wickline*1,2 Address: 1Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA and 2Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA Email: Emily A Waters - [email protected]; Junjie Chen - [email protected]; John S Allen - [email protected]; Huiying Zhang - [email protected]; Gregory M Lanza - [email protected]; Samuel A Wickline* - [email protected] * Corresponding author
Published: 25 September 2008 Journal of Cardiovascular Magnetic Resonance 2008, 10:43
doi:10.1186/1532-429X-10-43
Received: 24 January 2008 Accepted: 25 September 2008
This article is available from: http://www.jcmr-online.com/content/10/1/43 © 2008 Waters et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of ανβ3 integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets. Methods: New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with ανβ3 integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with ανβ3 integrin targeted PFC nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry. Results: Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated
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