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Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
Open accessAbstract
Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies.The αvβ3 integrin is expressed in angiogenic vessels and represents a potential novel target for imaging myocardial angiogenesis.We demonstrated the localization of an indium-111-labeled ( 111 In-labeled) αvβ3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction.The specificity of the targeted αvβ3-imaging agent for angiogenesis was established using a nonspecific control agent.The potential of this radiolabeled αvβ3-targeted agent for in vivo imaging was then confirmed in a canine model of postinfarction angiogenesis.Serial in vivo dual-isotope single-photon emission-computed tomographic (SPECT) imaging with the 111 In-labeled αvβ3-targeted agent demonstrated focal radiotracer uptake in hypoperfused regions where angiogenesis was stimulated.There was a fourfold increase in myocardial radiotracer uptake in the infarct region associated with histological evidence of angiogenesis and increased expression of the αvβ3 integrin.Thus, angiogenesis in the heart can be imaged noninvasively with an 111 In-labeled αvβ3-targeted agent.The noninvasive evaluation of angiogenesis may have important implications for risk stratification of patients following myocardial infarction.This approach may also have significant clinical utility for noninvasively tracking therapeutic myocardial angiogenesis.Nonstandard abbreviations used: indium-111 ( 111 In); iodine-125 ( 125 I); left anterior descending (LAD); magnetic resonance (MR); 2-methoxy-2-methylpropyl-isonitrile (sestamibi); positron emission tomography (PET); single-photon emission-computed tomographic (SPECT); Technetium-99m ( 99m Tc); thallium-201 ( 201 Tl); 2,3,5-triphenyl-2H-tetrazolium chloride (TTC).Conflict of interest: D.S. Edwards, S. Liu, and T.D. Harris were employees of Bristol-Myers Squibb at the time the studies were performed.
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Cites
Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels
Brooks, P. C., Montgomery, A. M. P., Rosenfeld, M., Reisfeld, R. A., Hu, T., Klier, G., & Cheresh, D. A. (1994) · Cell · doi:10.1016/0092-8674(94)90007-8 · Cited by 2,262
Cited by
Winter, P. M., Neubauer, A. M., Caruthers, S. D., Harris, T. D., Robertson, J. D., Williams, T. A., Schmieder, A. H., Hu, G., Allen, J. S., Lacy, E. K., et al. (2006) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000235724.11299.76 · Cited by 379
Self-citationLiu, S. (2009) · Bioconjugate Chemistry · doi:10.1021/bc900167c · Cited by 344
Self-citationLeuschner, F., & Nahrendorf, M. (2011) · Circulation Research · doi:10.1161/circresaha.110.232678 · Cited by 110
Metadata
- Authors
- Meoli, D. F., Sadeghi, M. M., Krassilnikova, S., Bourke, B. N., Giordano, F. J., Dione, D. P., Su, H., Edwards, D. S., Liu, S., Harris, T. D., Madri, J. A., Zaret, B. L., & Sinusas, A. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-06-15
- Volume
- 113
- Issue
- 12
- Pages
- 1684-1691
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2128559706
- Cited by
- 262
- References
- 1
- FWCI
- 15.51
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Meoli, D. F., Sadeghi, M. M., Krassilnikova, S., Bourke, B. N., Giordano, F. J., Dione, D. P., Su, H., Edwards, D. S., Liu, S., Harris, T. D., Madri, J. A., Zaret, B. L., & Sinusas, A. J. (2004). Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. Journal of Clinical Investigation. https://doi.org/10.1172/jci200420352
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