Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

• Published in: Radiology Vol. 280; no. 3; pp. 815 - 825
• Main Authors: Parashurama, Natesh, Ahn, Byeong-Cheol, Ziv, Keren, Ito, Ken, Paulmurugan, Ramasamy, Willmann, Jürgen K, Chung, Jaehoon, Ikeno, Fumiaki, Swanson, Julia C, Merk, Denis R, Lyons, Jennifer K, Yerushalmi, David, Teramoto, Tomohiko, Kosuge, Hisanori, Dao, Catherine N, Ray, Pritha, Patel, Manishkumar, Chang, Ya-Fang, Mahmoudi, Morteza, Cohen, Jeff Eric, Goldstone, Andrew Brooks, Habte, Frezghi, Bhaumik, Srabani, Yaghoubi, Shahriar, Robbins, Robert C, Dash, Rajesh, Yang, Phillip C, Brinton, Todd J, Yock, Paul G, McConnell, Michael V, Gambhir, Sanjiv S
• Format: Journal Article
• Language: English
• Published: United States Radiological Society of North America 01.09.2016
• Subjects: Animals; Female; Genes, Reporter; Luciferases, Firefly - metabolism; Luminescent Measurements; Mesenchymal Stem Cell Transplantation - methods; Mice; Mice, Nude; Molecular Imaging; Multimodal Imaging; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - therapy; Original Research; Positron-Emission Tomography; Transfection
• ISSN: 0033-8419; 1527-1315
• DOI: 10.1148/radiol.2016140049

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.