MRI of ICAM-1 upregulation after stroke: the importance of choosing the appropriate target-specific particulate contrast agent

Mol Imaging Biol. 2013 Aug;15(4):411-22. doi: 10.1007/s11307-013-0617-z.

Abstract

Purpose: Magnetic resonance imaging (MRI) with targeted contrast agents provides a promising means for diagnosis and treatment monitoring after cerebrovascular injury. Our goal was to demonstrate the feasibility of this approach to detect the neuroinflammatory biomarker intercellular adhesion molecule-1 (ICAM-1) after stroke and to establish a most efficient imaging procedure.

Procedures: We compared two types of ICAM-1-functionalized contrast agent: T 1-shortening gadolinium chelate-containing liposomes and T2(*)-shortening micron-sized iron oxide particles (MPIO). Binding efficacy and MRI contrast effects were tested in cell cultures and a mouse stroke model.

Results: Both ICAM-1-targeted agents bound effectively to activated cerebrovascular cells in vitro, generating significant MRI contrast-enhancing effects. Direct in vivo MRI-based detection after stroke was only achieved with ICAM-1-targeted MPIO, although both contrast agents showed similar target-specific vascular accumulation.

Conclusions: Our study demonstrates the potential of in vivo MRI of post-stroke ICAM-1 upregulation and signifies target-specific MPIO as most suitable contrast agent for molecular MRI of cerebrovascular inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain / pathology
  • Cell Line
  • Contrast Media*
  • Endothelial Cells / metabolism
  • Ferric Compounds
  • Gadolinium
  • Inflammation / pathology
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Liposomes
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Inbred C57BL
  • Particle Size
  • Particulate Matter*
  • Postmortem Changes
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stroke / diagnosis*
  • Stroke / genetics
  • Stroke / pathology
  • Up-Regulation / genetics*

Substances

  • Contrast Media
  • Ferric Compounds
  • Liposomes
  • Particulate Matter
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • ferric oxide
  • Gadolinium