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

作者:Wang Kezheng; Pan Dipanjan; Schmieder Anne H; Senpan Angana; Caruthers Shelton D; Cui Grace; Allen John S; Zhang Huiying; Shen Baozhong*; Lanza Gregory M
来源:Nanomedicine: Nanotechnology, Biology and Medicine , 2015, 11(3): 569-578.
DOI:10.1016/j.nano.2014.12.008

摘要

A high r1 relaxivity manganese-gadolinium nanocolloid (alpha(v)beta(3)-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12 months using a clinical MRI scanner (3 T). 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 alpha(v)beta(3)-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of alpha(v)beta(3)-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. alpha(v)beta(3)-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-GdNC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging.