A1 Refereed original research article in a scientific journal
Molecular Imaging of Early αvβ3 Integrin Expression Predicts Long-Term Left-Ventricle Remodeling After Myocardial Infarction in Rats
Authors: Sherif HM, Saraste A, Nekolla SG, Weidl E, Reder S, Tapfer A, Rudelius M, Higuchi T, Botnar RM, Wester HJ, Schwaiger M
Publisher: SOC NUCLEAR MEDICINE INC
Publication year: 2012
Journal: Journal of Nuclear Medicine
Journal name in source: JOURNAL OF NUCLEAR MEDICINE
Journal acronym: J NUCL MED
Number in series: 2
Volume: 53
Issue: 2
First page : 318
Last page: 323
Number of pages: 6
ISSN: 0161-5505
DOI: https://doi.org/10.2967/jnumed.111.091652
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.
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.
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