Characterization and in vitro and in vivo testing of CB2-receptor- and NGAL-targeted paramagnetic micelles for molecular MRI of vulnerable atherosclerotic plaque

Mol Imaging Biol. 2010 Dec;12(6):635-51. doi: 10.1007/s11307-010-0323-z.

Abstract

Purpose: Atherosclerotic plaque macrophages express the peripheral cannabinoid receptor (CB2-R) and promote fibrous cap degradation by secretion of neutrophil gelatinase-associated lipocalin 2 (NGAL). In this study, we report the preparation, characterization, and in vitro and in vivo testing of double-labeled (MR and fluorescent) CB2-R- and NGAL-targeted micelles.

Procedures/results: Specific CB2-R agonists or antibodies directed to 24p3 (mouse homolog of NGAL) were incorporated into di-oleoyl-polyethylene glycol-phosphatidylethanolamine 1000 (DOPE-PEG1000) micelles or di-stearoyl-polyethylene glycol-phosphatidylethanolamine 2000 (DSPE-PEG2000) micelles. The hydrodynamic diameter, determined by dynamic light scattering, was 16.5 and 19.0 nm for CB2-R-targeted DOPE-PEG1000 and DSPE-PEG2000 micelles, respectively, and 23.0 nm for Ab-conjugated DSPE-PEG2000 micelles. In vitro and in vivo MRI and fluorescence microscopy showed specific binding of CB2-R-targeted and 24p3-targeted micelles to in vitro systems and to aortic plaque in apoE(-/-)/eNOS(-/-) mice, respectively.

Conclusions: CB2-R- and NGAL-targeted micelles show promise as tools for in vivo characterization of vulnerable plaque.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / antagonists & inhibitors
  • Acute-Phase Proteins / metabolism*
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Feasibility Studies
  • Lipocalin-2
  • Lipocalins / antagonists & inhibitors
  • Lipocalins / metabolism*
  • Magnetic Resonance Imaging / methods*
  • Magnetics / methods
  • Mice
  • Mice, Knockout
  • Micelles*
  • Molecular Imaging / methods*
  • Molecular Targeted Therapy
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / metabolism*
  • Phosphatidylethanolamines / chemistry
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / metabolism
  • Polyethylene Glycols / chemistry
  • Radiography
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • 1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine
  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • Micelles
  • Oncogene Proteins
  • Phosphatidylethanolamines
  • Receptor, Cannabinoid, CB2
  • Lcn2 protein, mouse
  • Polyethylene Glycols