Molecular imaging of early αvβ3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats

Hossam M. Sherif, Antti Saraste, Stephan G. Nekolla, Eliane Weidl, Sybille Reder, Arne Tapfer, Martina Rudelius, Takahiro Higuchi, Rene M. Botnar, Hans-Juergen Wester, Markus Schwaiger

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62 Citations (Scopus)

Abstract

F-18-galacto-RGD (F-18-RGD) is a PET tracer binding to alpha(v)beta(3) integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial F-18-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. Methods: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with F-18-RGD to evaluate alpha(v)beta(3) integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by N-13-ammonia PET and MRI, respectively. Results: One week after MI, F-18-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 +/- 0.05 vs. 0.06 +/- 0.03 and 0.07 +/- 0.04, P <0.001). At this time, F-18-RGD uptake was associated with capillary density in histologic sections. Average F-18-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 +/- 0.07 vs. 0.21 +/- 0.05, P <0.05). In a multivariable logistic regression analysis, low F-18-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P <0.05). Conclusion: High levels of F-18-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that alpha(v)beta(3) integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.
Original languageEnglish
Pages (from-to)318 - 323
Number of pages6
JournalJournal of Nuclear Medicine
Volume53
Issue number2
DOIs
Publication statusPublished - 1 Feb 2012

Keywords

  • Ventricular Remodeling
  • Galactose
  • Magnetic Resonance Imaging
  • Animals
  • Integrin alphaVbeta3
  • Positron-Emission Tomography
  • Biological Transport
  • Rats
  • Peptides, Cyclic
  • Molecular Imaging
  • Rats, Wistar
  • Ventricular Dysfunction, Left
  • Gene Expression Regulation
  • Time Factors
  • Myocardial Infarction
  • Male

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