Abstract 20216: In vivo Mapping of Angiogenesis with Ultralow-Gadolinium Manganese Nanocolloids
Background: Angiogenesis is an integrative biomarker of atherosclerotic plaque, reflecting macrophage, T-cell and MMP activities. Sensitive detection of plaque angiogenesis has been reported using high payload (30mole%) gadolinium nanoparticles, but nephrogenic systemic fibrosis (NSF) in patients with severe renal disease has fueled efforts to lower gadolinium exposure.
Objective: The objective of the present project was to develop and demonstrate a high T1w antiangiogenic molecular imaging agent that decreased gadolinium exposure by > 95%.
Methods and Results: A new MR contrast agent (135 nm) with a chemically stable manganese-polysorbate core was found to have high relaxivity (r1) in suspension and high T1w contrast bound to fibrin-rich clot. To further increase r1 for sensitive detection of sparser neovascular receptors, such as αvβ3-integrin, supplemental lipophilic Gd-DOTA chelate was included in the Mn particle surfactant at 0.6 to 30mole%. r1 and r2 MR properties were characterized with MR pulse sequence techniques revealing that as little as 1.25mole% Gd added to the Mn particle optimized paramagnetic advantage at 3T (25°C): particulate r1=918,200(s·mmol)−1 with an ionic r1 of 394(s·mmol[Gd])−1; particulate r2 was 343,200(s·mmol)−1 with an ionic r2 of 147(s·mmol[Gd])−1. Pilot in vivo studies in a rat FGF/Matrigel model (n=2/group) (Fig) and in a larger Vx-2 rabbit tumor model (n=2/group) demonstrated the concept that αvβ3-targeted 1.25% Gd-Mn nanoparticles provide robust 3D mapping of angiogenesis, which was corroborated microscopically.
Conclusions: These data show that rapid, high resolution imaging of angiogenesis can be achieved with less than 1/100th of the gadolinium approved for Gd-DTPA blood pool imaging. As the biomarker role of angiogenesis in plaque evolves, this Gd-MN contrast agent offers MRI angiogenesis imaging with less risk of NSF likely.
- © 2010 by American Heart Association, Inc.