Imaging of VEGF receptor in a rat myocardial infarction model using PET

Martin Rodriguez-Porcel, Weibo Cai, Olivier Gheysens, Jürgen K. Willmann, Kai Chen, Hui Wang, Ian Y. Chen, Lina He, Joseph C. Wu, Zi Bo Li, Khalid A. Mohamedali, Sehoon Kim, Michael G. Rosenblum, Xiaoyuan Chen, Sanjiv Sam Gambhir

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79 Scopus citations

Abstract

Myocardial infarction (MI) leads to left ventricular (LV) remodeling, which leads to the activation of growth factors such as vascular endothelial growth factor (VEGF). However, the kinetics of a growth factor's receptor expression, such as VEGF, in the living subject has not yet been described. We have developed a PET tracer (64Cu-DOTA-VEGF121 [DOTA is 1,4,7,10-tetraazadodecane-N,N′,N″,N‴-tetraacetic acid]) to image VEGF receptor (VEGFR) expression after MI in the living subject. Methods: In Sprague-Dawley rats, MI was induced by ligation of the left coronary artery and confirmed by ultrasound (n = 8). To image and study the kinetics of VEGFRs, 64Cu-DOTA-VEGF121 PET scans were performed before MI induction (baseline) and on days 3, 10, 17, and 24 after MI. Sham-operated animals served as controls (n = 3). Results: Myocardial origin of the 64Cu-DOTA-VEGF121 signal was confirmed by CT coregistration and autoradiography. VEGFR specificity of the 64Cu-DOTA-VEGF121 probe was confirmed by in vivo use of a 64Cu-DOTA-VEGFmutant. Baseline myocardial uptake of 64Cu-DOTA-VEGF121 was minimal (0.30 ± 0.07 %ID/g [percentage injected dose per gram of tissue]); it increased significantly after MI (day 3, 0.97 ± 0.05 %ID/g; P < 0.05 vs. baseline) and remained elevated for 2 wk (up to day 17 afterMI), after which time it returned to baseline levels. Conclusion: We demonstrate the feasibility of imaging VEGFRs in the myocardium. In summary, we imaged and described the kinetics of 64Cu-DOTA-VEGF121 uptake in a rat model of MI. Studies such as the one presented here will likely play a major role when studying pathophysiology and assessing therapies in different animal models of disease and, potentially, in patients. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)667-673
Number of pages7
JournalJournal of Nuclear Medicine
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2008

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Keywords

  • Angiogenesis
  • Cu
  • Myocardial infarction
  • PET
  • VEGF receptor (VEGFR)
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Rodriguez-Porcel, M., Cai, W., Gheysens, O., Willmann, J. K., Chen, K., Wang, H., Chen, I. Y., He, L., Wu, J. C., Li, Z. B., Mohamedali, K. A., Kim, S., Rosenblum, M. G., Chen, X., & Gambhir, S. S. (2008). Imaging of VEGF receptor in a rat myocardial infarction model using PET. Journal of Nuclear Medicine, 49(4), 667-673. https://doi.org/10.2967/jnumed.107.040576