Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction

Leszek Kalinowski, Lawrence W. Dobrucki, David F. Meoli, Donald P. Dione, Mehran M. Sadeghi, Joseph A. Madri, Albert J. Sinusas

Research output: Contribution to journalArticlepeer-review


The αvβ3-integrin is expressed in angiogenic vessels in response to hypoxia and represents a potential novel target for imaging myocardial angiogenesis. This study evaluated the feasibility of noninvasively tracking hypoxia-induced αvβ3-integrin activation within the myocardium as a marker of angiogenesis early after myocardial infarction. Acute myocardial infarction was produced by coronary artery occlusion in rodent and canine studies. A novel 111In-labeled radiotracer targeted at the αvβ3-integrin (111In-RP748) was used to localize regions of hypoxia-induced angiogenesis early after infarction. In rodent studies, the specificity of 111In-RP748 for αvβ3-integrin was confirmed with a negative control compound (111In-RP790), and regional uptake of these compounds correlated with 201Tl perfusion and a 99mTc-labeled nitroimidazole (BRU59-21), which was used as a quantitative marker of myocardial hypoxia. The ex vivo analysis demonstrated that only 111In-RP748 was selectively retained in infarcted regions with reduced 201Tl perfusion and correlated with uptake of BRU59-21. In canine studies, myocardial uptake of 111In-RP748 was assessed using in vivo single-photon-emission computed tomography (SPECT), ex vivo planar imaging, and gamma well counting of myocardial tissue and correlated with 99mTc-labeled 2-methoxy-2-methyl-propylisonitrile ( 99mTc-sestamibi) perfusion. Dual-radiotracer in vivo SPECT imaging of 111In-RP748 and 99mTc-sestamibi provided visualization of 111In-RP748 uptake within the infarct region, which was confirmed by ex vivo planar imaging of excised myocardial slices. Myocardial 111In-RP748 retention was associated with histological evidence of αvβ3-integrin expression/activation in the infarct region. 111In-RP748 imaging provides a novel noninvasive approach for evaluation of hypoxia-induced αvβ3-integrin activation in myocardium early after infarction and may prove useful for directing and evaluating angiogenic therapies in patients with ischemic heart disease.

Original languageEnglish (US)
Pages (from-to)1504-1512
Number of pages9
JournalJournal of Applied Physiology
Issue number5
StatePublished - May 2008
Externally publishedYes


  • Angiogenesis
  • Myocardial infarction
  • Radiotracer imaging

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation


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