Abstract 4709: Targeted Microbubble Imaging of Matrix Metalloproteinase-2 in Post-Infarction Rat Model: in vitro and in vivo Studies
Activation of matrix metalloproteinase2 (MMP2) after myocardial infarction (MI) contributes to adverse left ventricular remodeling. We hypothesized that post MI remodeling associated MMP2 activation could be detected by using novel MMP2 targeted ultrasound imaging. MMP2 targeted microbubbles (TMB2) were prepared by conjugating monoclonal MMP2 antibody to microbubble shell using the poly ethylene glycol (PEG) arm. Control MB (MBc) was also prepared. Attachment of antibodies to the MB’s surface was verified by flow cytometry and fluorescent microscopy studies. In vitro studies, TMB2 significantly bound within the risk area (RA) of one-week post MI myocardial sections (Figure 1A⇓), while rare binding was observed in the control area (CA). Neither TMB2 nor MBc bound to myocardial tissue in control rats. In vivo studies, triggered myocardial contrast echocardiography was performed to increase microvascular permeability. Subsequently, MBc or TMB2 was intravenously administered. In one week post-MI rats, increased focal retention of TMB2 was observed within the RA (Figure 1B⇓), with the higher myocardial video intensity (RA: 42.85dB ± 20.12dB versus CA: 25.85 dB ± 13.40dB, p <0.01). However, there was no difference of MBc retention in both CA and RA. There was no obvious retention of either TMB2 or MBc in control rats. Targeted ultrasound contrast imaging approach that employs novel MMP2-targeted microbubbles has the potential to provide a less-invasive, higher-resolution technique for in vivo localization of MMP2 activation and tracking of MMP-mediated post-MI remodeling.