MRI of High-Glucose Metabolism Tumors: a Study in Cells and Mice with 2-DG-Modified Superparamagnetic Iron Oxide Nanoparticles.

Abstract

PurposeThis study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe2O3@DMSA) bearing the 2-deoxy-d-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism.Proceduresγ-Fe2O3@DMSA and 2-DG-conjugated γ-Fe2O3@DMSA (γ-Fe2O3@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with γ-Fe2O3@DMSA or γ-Fe2O3@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo.ResultsGlucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe2O3@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe2O3@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe2O3@DMSA in either cell line. In vivo, γ-Fe2O3@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe2O3@DMSA was nearly undetectable in tumors.Conclusions2-DG-coated γ-Fe2O3@DMSA improved tumor targeting of γ-Fe2O3@DMSA which can be assessed by magnetic resonance imaging.