PET imaging of cardiac wound healing using a novel [68Ga]-labeled NGR probe in rat myocardial infarction

Mol Imaging Biol. 2015 Feb;17(1):76-86. doi: 10.1007/s11307-014-0751-2. Epub 2014 Jul 11.

Abstract

Purpose: Peptides containing the asparagine-glycine-arginine (NGR) motif bind to aminopeptidase N (CD13), which is expressed on inflammatory cells, endothelial cells, and fibroblasts. It is unclear whether radiolabeled NGR-containing tracers could be used for in vivo imaging of the early wound-healing phase after myocardial infarction (MI) using positron emission tomography (PET).

Procedures: Uptake of novel tracer [(68)Ga]NGR was assessed together with [(68)Ga]arginine-glycine-aspartic acid ([(68)Ga]RGD) and 2-deoxy-2-[(18) F]fluoro-D-glucose after myocardial ischemia/reperfusion (MI/R) injury using μ-PET and autoradiography, and relative expressions of CD13 and integrin β3 were assessed in fibroblasts, inflammatory cells, and endothelial cells by immunohistochemistry.

Results: In the infarcted myocardium, uptake of [(68)Ga]NGR was maximal from days 3 to 7 after MI/R, and correlated with fibroblast and inflammatory cell infiltration as well as [(68)Ga]RGD uptake.

Conclusions: [(68)Ga]NGR allows noninvasive and sequential determination of CD13 expression in fibroblasts and inflammatory cells by PET. This will facilitate monitoring of CD13 in the individual wound healing processes, allowing patient-specific therapies to improve outcome after MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • CD13 Antigens / metabolism
  • Fibroblasts / diagnostic imaging
  • Fibroblasts / pathology
  • Gallium Radioisotopes
  • Heart / diagnostic imaging*
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Male
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Ischemia / diagnostic imaging
  • Myocardium / pathology
  • Oligopeptides / chemistry
  • Positron-Emission Tomography*
  • Rats
  • Rats, Wistar
  • Wound Healing

Substances

  • Gallium Radioisotopes
  • NGR peptide
  • Oligopeptides
  • CD13 Antigens