Molecular Imaging of Early α v β 3 Integrin Expression Predicts Long-Term Left-Ventricle Remodeling After Myocardial Infarction in Rats

18F-galacto-RGD (18F-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 18F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a ra...

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Veröffentlicht in:Journal of Nuclear Medicine 2012-02, Vol.53 (2), p.318-323
Hauptverfasser: Sherif, Hossam M., Saraste, Antti, Nekolla, Stephan G., Weidl, Eliane, Reder, Sybille, Tapfer, Arne, Rudelius, Martina, Higuchi, Takahiro, Botnar, René M., Wester, Hans-Jürgen, Schwaiger, Markus
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Sprache:eng
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Zusammenfassung:18F-galacto-RGD (18F-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 18F-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 18F-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 13N-ammonia PET and MRI, respectively. RESULTS: One week after MI, 18F-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 plus or minus 0.05 vs. 0.06 plus or minus 0.03 and 0.07 plus or minus 0.04, P < 0.001). At this time, 18F-RGD uptake was associated with capillary density in histologic sections. Average 18F-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 plus or minus 0.07 vs. 0.21 plus or minus 0.05, P < 0.05). In a multivariable logistic regression analysis, low 18F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). CONCLUSION: High levels of 18F-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.
ISSN:0161-5505
2159-662X
DOI:10.2967/jnumed.111.091652