Chelator-Free 99mTc-Labeled Yttrium Oxide Nanoparticles for Dose-Dependent Early Biodistribution Tracking in Mice.

Yttrium oxide (Y2O3), as a rare-earth oxide nanoparticle, has potential toxicity that remains unresolved. By bridging the gap between nanomaterial development and safety assessment, this work aimed to evaluate the biodistribution of Y2O3 using a novel radiolabeling approach with technetium-99m (99mTc) for real-time tracking. Different concentrations (0.4, 4, and 8 mg/mL) of Y2O3 were used for 99mTc labeling and were intravenously administered to mice. In vivo organ biodistribution was measured via dynamic planar imaging and micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT). Biodistribution and inductively coupled plasma mass spectrometry (ICP-MS) were conducted to quantitative tissue uptake of 99mTc-Y2O3, and hematoxylin-eosin (H&E) staining were performed for histopathological evaluation. Different concentrations of 99mTc-Y2O3 were successfully synthesized with a high radiochemical purity and stability. In vivo imaging revealed different distribution patterns with 0.4, 4, and 8 mg/mL of 99mTc-Y2O3. Low-dose 99mTc-Y2O3 nanoparticles rapidly cleared from pulmonary circulation, shifting to predominant hepatic-splenic accumulation. In contrast, medium and high doses demonstrated prolonged lung retention with partial redistribution to the spleen and liver. These biodistribution patterns were validated by ICP-MS, which showed a strong correlation with the 99mTc-Y2O3 tracking. Histopathology revealed dose-related alveolar wall thickening and splenic white pulp expansion. This study demonstrated that 99mTc-Y2O3 could be a robust tool for nanoparticle in vivo tracking, providing the organ distribution information for long-term toxicity studies and chronic exposure effects.