Oligoethylenimine-grafted chitosan as enhanced T1 contrast agent for in vivo targeted tumor MRI

J Magn Reson Imaging. 2016 Jul;44(1):23-9. doi: 10.1002/jmri.25141. Epub 2015 Dec 29.

Abstract

Purpose: To synthesize and characterize an effective macromolecular magnetic resonance imaging (MRI) contrast agent based on oligoethylenimine-grafted chitosan with targeting capability.

Materials and methods: In this study we synthesized and characterized oligoethylenimine-grafted chitosan copolymers, followed by conjugating with Gd-DTPA and folic acid. The toxicity was evaluated by WST assay, and in vitro MRI studies were performed in comparison with Gd-DTPA. Finally, the contrast enhancement of the new macromolecular MRI contrast agent was then evaluated in the mice bearing KB xenografts.

Results: Compared to Gd-DTPA (4.3 mM(-1) s(-1) ), this macromolecular contrast agent (mCA) exhibited much higher T1 relaxivity (14.4 mM(-1) s(-1) ), up to 3.3 times higher. Meanwhile, the WST assay illustrated that the viability of KB cells remained at 90% even when the Gd concentration was 1 mM. During the in vivo study, the image contrast produced by FA-mCA was higher than one produced by mCA, up to 2.5 times higher.

Conclusion: Our results showed this macromolecular contrast agent has potential for developing sensitive and biocompatible MRI probe with targeting capability. J. Magn. Reson. Imaging 2016;44:23-29.

Keywords: chitosan; macromolecular contrast agent; oligoethylenimine; targeted tumor imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aziridines / chemistry
  • Cell Line, Tumor
  • Chitosan / chemistry*
  • Contrast Media / chemical synthesis
  • Folate Receptors, GPI-Anchored / metabolism*
  • Folic Acid / chemistry
  • Folic Acid / pharmacokinetics*
  • Gadolinium DTPA / chemistry
  • Gadolinium DTPA / pharmacokinetics*
  • Image Enhancement / methods
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Nude
  • Molecular Probe Techniques
  • Neoplasms, Experimental / diagnostic imaging*
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Aziridines
  • Contrast Media
  • Folate Receptors, GPI-Anchored
  • aziridine
  • Chitosan
  • Folic Acid
  • Gadolinium DTPA