Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent

Biomacromolecules. 2015 Sep 14;16(9):2964-71. doi: 10.1021/acs.biomac.5b00867. Epub 2015 Aug 25.

Abstract

Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd-CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Contrast Media* / chemistry
  • Contrast Media* / pharmacology
  • Gadolinium* / chemistry
  • Gadolinium* / pharmacology
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / diagnostic imaging*
  • Polysaccharides* / chemistry
  • Polysaccharides* / pharmacology
  • Radiography

Substances

  • Contrast Media
  • Polysaccharides
  • Gadolinium