Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction.
Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The alphavbeta3 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) alphavbeta3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted alphavbeta3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled alphavbeta3-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 alphavbeta3-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 alphavbeta3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an (111)In-labeled alphavbeta3-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.
Meoli
David F
DF
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8017, USA.
Sadeghi
Mehran M
MM
Krassilnikova
Svetlana
S
Bourke
Brian N
BN
Giordano
Frank J
FJ
Dione
Donald P
DP
Su
Haili
H
Edwards
D Scott
DS
Liu
Shuang
S
Harris
Thomas D
TD
Madri
Joseph A
JA
Zaret
Barry L
BL
Sinusas
Albert J
AJ
D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000378:metabolism*; D003952:Diagnostic Imaging; D004285:Dogs; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006439:Hemodynamics; D007205:Indium Radioisotopes / Q000737:chemistry / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D009203:Myocardial Infarction; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3; D015363:Quinolones; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi