Molecular imaging of early α vβ 3 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, René M. Botnar, Hans Jürgen Wester, Markus Schwaiger

Research output: Contribution to journalArticle

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Abstract

18F-galacto-RGD ( 18F-RGD) is a PET tracer binding to α vβ 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 α vβ 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 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 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 ± 0.07 vs. 0.21 ± 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 18FRGD 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 α vβ 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 - Feb 1 2012
Externally publishedYes

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Ventricular Remodeling
Molecular Imaging
Integrins
Myocardial Infarction
Heart Ventricles
fluorogalacto-RGD
Ammonia
Ligation
Wistar Rats
Myocardium
Perfusion
Biomarkers
Logistic Models
Regression Analysis

Keywords

  • F-galacto-RGD
  • LV remodeling
  • MRI
  • Myocardial infarction
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Molecular imaging of early α vβ 3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats. / 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.

In: Journal of Nuclear Medicine, Vol. 53, No. 2, 01.02.2012, p. 318-323.

Research output: Contribution to journalArticle

Sherif, HM, Saraste, A, Nekolla, SG, Weidl, E, Reder, S, Tapfer, A, Rudelius, M, Higuchi, T, Botnar, RM, Wester, HJ & Schwaiger, M 2012, 'Molecular imaging of early α vβ 3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats', Journal of Nuclear Medicine, vol. 53, no. 2, pp. 318-323. https://doi.org/10.2967/jnumed.111.091652
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. / Molecular imaging of early α vβ 3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats. In: Journal of Nuclear Medicine. 2012 ; Vol. 53, No. 2. pp. 318-323.
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abstract = "18F-galacto-RGD ( 18F-RGD) is a PET tracer binding to α vβ 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 α vβ 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 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 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 ± 0.07 vs. 0.21 ± 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 18FRGD 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 α vβ 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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AU - Sherif, Hossam M.

AU - Saraste, Antti

AU - Nekolla, Stephan G.

AU - Weidl, Eliane

AU - Reder, Sybille

AU - Tapfer, Arne

AU - Rudelius, Martina

AU - Higuchi, Takahiro

AU - Botnar, René M.

AU - Wester, Hans Jürgen

AU - Schwaiger, Markus

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N2 - 18F-galacto-RGD ( 18F-RGD) is a PET tracer binding to α vβ 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 α vβ 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 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 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 ± 0.07 vs. 0.21 ± 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 18FRGD 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 α vβ 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.

AB - 18F-galacto-RGD ( 18F-RGD) is a PET tracer binding to α vβ 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 α vβ 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 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 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 ± 0.07 vs. 0.21 ± 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 18FRGD 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 α vβ 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.

KW - F-galacto-RGD

KW - LV remodeling

KW - MRI

KW - Myocardial infarction

KW - PET

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