Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction

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dc.citation.articleNumber1004202en_US
dc.citation.journalTitleSPIE Proceedingsen_US
dc.contributor.authorZhu, Bangheen_US
dc.contributor.authorGuenther, Caitlinen_US
dc.contributor.authorKwon, Sunkuken_US
dc.contributor.authorSevick-Muraca, Eva M.en_US
dc.contributor.authorSuh, Junghaeen_US
dc.date.accessioned2017-03-07T17:07:15Zen_US
dc.date.available2017-03-07T17:07:15Zen_US
dc.date.issued2017en_US
dc.description.abstractCardiovascular diseases remain the greatest cause of death in the US and gene therapy has the potential to be an effective therapy. In this study, we demonstrated MMP-9 based protease-activatable virus (PAV) for selective infection of myocardial infarct (MI) that is associated with active MMP-9 expression. To test the specificity of PAV, we used expression of a far-red fluorescence protein (iRFP) delivered by the PAV together with a dual PET/NIRF imaging agent specific for active MMP-9 activity at the site of MI in a murine model. Calibrated fluorescence imaging employed a highly-sensitive intensified camera, laser diode excitation sources, and filtration schemes based upon the spectra of iRFP and the NIRF agent. One to two days after ligation of the left anterior descending artery, the PAV or WT AAV9 virus encoding for iRFP (5x1010 genomic particles) and radiolabeled MMP-9 imaging agent (3 nmol) were injected intravenously (i.v.). PET imaging showed MMP activity was associated with adverse tissue remodeling at the site of the MI. One week after, animals were again injected i.v. with the MMP-9 agent (3 nmol) and 18-24 h later, the animals were euthanized and the hearts were harvested, sliced, and imaged for congruent iRFP transgene expression and NIRF signals associated with MMP-9 tissue activity. The fluorescent margins of iRFP and NIRF contrasted tissues were quantified in terms Standard International units of mW/cm2/sr. The sensitivity, specificity, and accuracy of PAV and WT targeting to sites of MI was determined from these calibrated fluorescence measurements. The PAV demonstrated significantly higher delivery performance than that of the WT AAV9 virus.en_US
dc.identifier.citationZhu, Banghe, Guenther, Caitlin, Kwon, Sunkuk, et al.. "Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction." <i>SPIE Proceedings,</i> (2017) SPIE: http://dx.doi.org/10.1117/12.2256760.en_US
dc.identifier.doihttp://dx.doi.org/10.1117/12.2256760en_US
dc.identifier.urihttps://hdl.handle.net/1911/94018en_US
dc.language.isoengen_US
dc.publisherSPIEen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.titleUsing molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarctionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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