Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin α4β1

Sci Rep. 2018 Feb 27;8(1):3733. doi: 10.1038/s41598-018-21893-x.

Abstract

Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in atherosclerotic plaques, especially in the coronary arteries. To address this, we have developed a clinically relevant system to image overall inflammatory cell burden in plaque. Here, we describe a targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable for magnetic resonance (MR) imaging and binds with high affinity and selectivity to the integrin α4β1(very late antigen-4, VLA-4), a key integrin involved in recruiting inflammatory cells to atherosclerotic plaques. This liposomal contrast agent has a high T1 relaxivity (~2 × 105 mM-1s-1 on a particle basis) resulting in the ability to image liposomes at a clinically relevant MR field strength. We were able to visualize atherosclerotic plaques in various regions of the aorta in atherosclerosis-prone ApoE-/- mice on a 1 Tesla small animal MRI scanner. These enhanced signals corresponded to the accumulation of monocyte/macrophages in the subendothelial layer of atherosclerotic plaques in vivo, whereas non-targeted liposomal nanoparticles did not demonstrate comparable signal enhancement. An inflammatory cell-targeted method that has the specificity and sensitivity to measure the inflammatory burden of a plaque could be used to noninvasively identify patients at risk of an acute ischemic event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Integrin alpha4beta1 / antagonists & inhibitors
  • Integrin alpha4beta1 / chemistry*
  • Integrin alpha4beta1 / metabolism*
  • Ligands
  • Liposomes
  • Magnetic Resonance Imaging* / methods
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Molecular Conformation
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Integrin alpha4beta1
  • Ligands
  • Liposomes