Nanomedicine: Nanotechnology, Biology and Medicine 2015-04-01

Atherosclerotic neovasculature MR imaging with mixed manganese-gadolinium nanocolloids in hyperlipidemic rabbits.

Kezheng Wang, Dipanjan Pan, Anne H Schmieder, Angana Senpan, Shelton D Caruthers, Grace Cui, John S Allen, Huiying Zhang, Baozhong Shen, Gregory M Lanza

Index: Nanomedicine: Nanotechnology, Biology, and Medicine 11(3) , 569-78, (2015)

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Abstract

A high r1 relaxivity manganese-gadolinium nanocolloid (αvβ3-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12 months using a clinical MRI scanner (3T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent αvβ3-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of αvβ3-integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile-fecal and renal excretion routes. αvβ3-MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis. From the clinical editor: Cerebrovascular accidents are a leading cause of mortality and morbidity worldwide. The acute formation of thrombus following atherosclerotic plaque rupture has been well recognized as the etiology of stroke. The authors studied microanatomical features of vulnerable atherosclerotic plaque in this article, in an attempt to identify those with high risk of rupture. Gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging.Copyright © 2015 Elsevier Inc. All rights reserved.