Targeted ultrasound contrast imaging of matrix metalloproteinase-2 in ischemia-reperfusion rat model: ex vivo and in vivo studies.
OBJECTIVE
We hypothesized that post-myocardial ischemia-reperfusion (I/R) remodeling associated matrix metalloproteinase-2 (MMP(2)) activation could be detected by using novel MMP(2) targeted ultrasound imaging.


METHODS
We study the combination of MMP(2)-targeted microbubbles (TMB(2)) and control microbubbles with myocardium in 1 week post-I/R rats.


RESULTS
In in vitro studies, TMB(2) significantly bound within the risk area (RA) of 1-week post-I/R myocardial sections while rare binding was observed in the control area (CA). In in vivo studies, increased focal retention of TMB(2) was observed within the RA, with the higher myocardial video intensity (RA 42.85 ± 20.12 dB versus CA 25.85 ± 13.40 dB, p < 0.01). However, there was no difference of control microbubble retention in both CA and RA.


CONCLUSIONS
A targeted ultrasound contrast imaging approach that employs novel TMB(2) has the potential to provide a less-invasive, higher-resolution technique for in vivo localization of MMP(2) activation and tracking of MMP-mediated post-I/R remodeling.
Su
Haili
H
Department of Ultrasound, Xijing Hospital, Fourth Military Med University, Xi'an, Shann Xi, China. suhaili@fmmu.edu.cn
Du
Yongfeng
Y
Qian
Yunqiu
Y
Zong
Yujin
Y
Li
Jun
J
Zhuang
Ran
R
He
Jianguo
J
Wei
Zhangrui
Z
Zhang
Jun
J
Zhou
Xiaodong
X
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000915:Antibody Affinity / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D045423:Microbubbles; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D057054:Molecular Imaging / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014465:Ultrasonics / Q000379:methods*; D016277:Ventricular Function, Left / Q000187:drug effects
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2