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

Banghe Zhu; Caitlin Guenther; Sunkuk Kwon; Eva M. Sevick-Muraca; Junghae Suh

doi:10.1117/12.2256760

8 February 2017 Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction

Banghe Zhu, Caitlin Guenther, Sunkuk Kwon, Eva M. Sevick-Muraca, Junghae Suh

Author Affiliations +

Proceedings Volume 10042, Diagnostic and Therapeutic Applications of Light in Cardiology; 1004202 (2017) https://doi.org/10.1117/12.2256760
Event: SPIE BiOS, 2017, San Francisco, California, United States

Abstract

Cardiovascular 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.

Conference Presentation

Citation Download Citation

Banghe Zhu, Caitlin Guenther, Sunkuk Kwon, Eva M. Sevick-Muraca, and Junghae Suh "Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction", Proc. SPIE 10042, Diagnostic and Therapeutic Applications of Light in Cardiology, 1004202 (8 February 2017); https://doi.org/10.1117/12.2256760

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available