Multimodal Gadolinium Oxysulfide Nanoparticles for Bioimaging: A Comprehensive Biodistribution, Elimination and Toxicological Study

Abstract

For some years now, gadolinium oxysulfide nanoparticles (NPs) appear as strong candidates for very efficient multimodal in vivo imaging by: 1) Magnetic Resonance (MRI), 2) X-ray Computed Tomography (CT) and 3) photoluminescence imaging. In this paper, we present a selection of results centered on the evaluation of physico-chemical stability, toxicity, bio-distribution and excretion mechanisms of Gd2O2S:Ln3+ nanoparticles intravenously injected in rats. Two formulations are here tested with a common matrix and different dopants: Gd2O2S:Eu3+5% and Gd2O2S:Yb3+4%/Tm3+0.1%. The NPs appear to be almost insoluble in pure water and human plasma but corrosion/degradation phenomenon appears in acidic conditions classically encountered in cell lysosomes. Whole body in vivo distribution, excretion and toxicity evaluation revealed a high tolerance of nanoparticles with a long-lasting imaging signal associated with a slow hepatobiliary clearance and very weak urinary excretion. The results show that the majority of the injected product (> 60%) has been excreted through the feces after five months. Experiments have evidenced that the NPs mainly accumulate in macrophage-rich organs, that is mainly liver and spleen and to a lesser extent lungs and bones (mainly marrow). No significant amounts have been detected in other organs such as heart, kidneys, brain, intestine and skin. Gd2O2S:Ln3+ NPs appeared to be very well tolerated up to 400 mg/kg when administered intravenously.