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

Mol Imaging Biol. 2016 Feb;18(1):24-33. doi: 10.1007/s11307-015-0874-0.

Abstract

Purpose: This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe(2)O(3)@DMSA) bearing the 2-deoxy-D-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism.

Procedures: γ-Fe(2)O(3)@DMSA and 2-DG-conjugated γ-Fe(2)O(3)@DMSA (γ-Fe(2)O(3)@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-Fe(2)O(3)@DMSA or γ-Fe(2)O(3)@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.

Results: Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe(2)O(3)@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe(2)O(3)@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe(2)O(3)@DMSA in either cell line. In vivo, γ-Fe(2)O(3)@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe(2)O(3)@DMSA was nearly undetectable in tumors.

Conclusions: 2-DG-coated γ-Fe(2)O(3)@DMSA improved tumor targeting of γ-Fe(2)O(3)@DMSA which can be assessed by magnetic resonance imaging.

Keywords: 2-Deoxy-D-glucose; Breast cancer; Glucose metabolism; Magnetic resonance imaging; Superparamagnetic iron oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Deoxyglucose / metabolism*
  • Dextrans / metabolism*
  • Female
  • Frozen Sections
  • Glucose / metabolism*
  • Humans
  • Iron / metabolism
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry
  • Staining and Labeling
  • Succimer / chemistry
  • Succimer / metabolism

Substances

  • Dextrans
  • Magnetite Nanoparticles
  • Deoxyglucose
  • Succimer
  • Iron
  • ferumoxides
  • Glucose