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

Natesh Parashurama, Byeong Cheol Ahn, Keren Ziv, Ken Ito, Ramasamy Paulmurugan, Jürgen K. Willmann, Jaehoon Chung, Fumiaki Ikeno, Julia C. Swanson, Denis R. Merk, Jennifer K. Lyons, David Yerushalmi, Tomohiko Teramoto, Hisanori Kosuge, Catherine N. Dao, Pritha Ray, Manishkumar Patel, Ya Fang Chang, Morteza Mahmoudi, J. E. CohenA. B. Goldstone, F. Habte, S. Bhaumik, S. Yaghoubi, R. C. Robbins, R. Dash, P. C. Yang, T. J. Brinton, P. G. Yock, M. V. McConnell, S. S. Gambhir

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalRadiology
Volume280
Issue number3
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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