Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles

Ultra-small gadolinium oxide nanoparticles (US-Gd2O3) are used to provide ` positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd2O3 particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with H-1 NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r(1)) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r(2)) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd2O3 as an efficient ` positive-T-1' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.