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.articleNumber1004202
dc.citation.journalTitleSPIE Proceedings
dc.contributor.authorZhu, Banghe
dc.contributor.authorGuenther, Caitlin
dc.contributor.authorKwon, Sunkuk
dc.contributor.authorSevick-Muraca, Eva M.
dc.contributor.authorSuh, Junghae
dc.date.accessioned2017-03-07T17:07:15Z
dc.date.available2017-03-07T17:07:15Z
dc.date.issued2017
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1117/12.2256760
dc.identifier.urihttps://hdl.handle.net/1911/94018
dc.language.isoeng
dc.publisherSPIE
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.
dc.titleUsing molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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