Polyethylene glycol-covered ultra-small Gd2O3 nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

摘要

The size distribution and magnetic properties of ultra- small gadolinium oxide crystals (US-Gd2O3) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r(1), r(2)) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd2O3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol ( DEG)-capped US-Gd2O3 nanocrystals were reacted with PEG-silane ( MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering ( DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG-Gd2O3 and PEG-silane-SPGO (Gd2O3, < 40 nm diameter). The small and narrow size distribution of US-Gd2O3 was confirmed with TEM (similar to 3 nm) and DLS. PEG-silane-US-Gd2O3 relaxation parameters were twice as high as for Gd-DTPA and the r(2)/r(1) ratio was 1.4. PEG-silane-SPGO gave low r(1) relaxivities and high r(2)/r(1) ratios, less compatible with positive contrast agent requirements. Higher r(1) were obtained with PEG-silane in comparison to DEG-Gd2O3. Treatment of DEG-US-Gd2O3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG- covered Gd2O3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.