Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography

Cardiovasc Res. 2008 May 1;78(2):395-403. doi: 10.1093/cvr/cvn033. Epub 2008 Feb 6.

Abstract

Aims: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction.

Methods and results: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion.

Results: PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis.

Conclusion: Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Coronary Vessels / diagnostic imaging*
  • Coronary Vessels / metabolism
  • Coronary Vessels / physiopathology
  • Disease Models, Animal
  • Feasibility Studies
  • Galactose / analogs & derivatives
  • Galactose / metabolism
  • Immunohistochemistry
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / metabolism*
  • Male
  • Myocardial Infarction / diagnostic imaging*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Neovascularization, Physiologic*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Integrin alphaVbeta3
  • Peptides, Cyclic
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Radiopharmaceuticals
  • cyclo(arginyl-glycyl-aspartyl-phenylalanyl-valyl)
  • fluorogalacto-RGD
  • Galactose