Stable and non-toxic ultrasmall gadolinium oxide nanoparticle colloids (coating material = polyacrylic acid) as high-performance T1 magnetic resonance imaging contrast agents

Abstract

For use as positive (T₁) magnetic resonance imaging contrast agents (MRI-CAs), gadolinium oxide (Gd₂O₃) nanoparticle colloids (i.e. nanoparticles coated with hydrophilic ligands) should be stable, non-toxic, and ultrasmall in particle diameter for renal excretion. In addition, they should have a high longitudinal water proton relaxivity (r₁) and r₂/r₁ ratio that is close to one (r₂ = transverse water proton relaxivity) for high-performance. In this study, we report ultrasmall Gd₂O₃ nanoparticle colloids [coating material = polyacrylic acid, M_w = ∼5100 Da] satisfying these conditions. The particle diameter was monodisperse with an average value of 2.0 ± 0.1 nm. The colloidal suspension exhibited a high r₁ value of 31.0 ± 0.1 s⁻¹ mM⁻¹ and r₂/r₁ ratio of 1.2, where r₁ was ∼8 times higher than that of commercial Gd-chelates: the cooperative induction model was proposed to explain this. The effectiveness of the colloidal suspension as a high-performance T₁ MRI-CA was confirmed by taking in vivo T₁ MR images in a mouse after intravenous administration. Highly positive contrast enhancements were observed in various organs of the mouse such as the liver, kidneys, and bladder. The colloidal suspension was then excreted through the bladder.