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Noninvasive radionuclide imaging of cardiac gene therapy: progress and potential

Nature Clinical Practice Cardiovascular Medicine volume 5, pages S87–S95 (2008)Cite this article

Abstract

Over the past decade, several clinical trials have evaluated the efficacy of cardiac-specific gene therapy. Despite encouraging results in basic research and preclinical studies, most of the recent large, randomized, placebo-controlled cardiac gene therapy trials have failed to provide convincing evidence of improvements in clinical outcomes. Because many of these problems are due to the lack of appropriate monitoring techniques, there is a critical need to develop noninvasive imaging techniques that can verify vector delivery and gene expression in target and nontarget tissues. The field of molecular imaging of cardiac gene expression is rapidly advancing because it offers distinct advantages over conventional methods, including the ability to noninvasively measure the location, time course, and magnitude of gene expression. We aim to give readers a clear understanding of how molecular imaging can enable noninvasive tracking of cardiac gene transfer and expression. We discuss limitations of current methods for analyzing gene transfer and describe how reporter gene imaging works.

Key Points

  • Molecular imaging has enabled the visual representation, characterization, and noninvasive quantification of biological processes within intact living organisms

  • Molecular imaging, specifically reporter gene imaging, can be used to track cardiac-specific gene transfer and expression during cardiovascular research

  • Strategies for imaging reporter gene–reporter probe interaction include enzyme-based reporters and receptor-based reporters

  • Reporter gene imaging can be applied in cardiovascular medicine to imaging gene expression, myocardial angiogenesis, outcome of vascular endothelial growth factor therapy, and conditional gene activation

  • The use of reporter genes and labeled reporter probes for noninvasive imaging is a good candidate methodology to address critical problems in cardiac gene therapy, such as vectors, delivery routes, targeting expression, and therapeutic efficacy

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Figure 1: Strategies for imaging reporter gene and reporter probe.
Figure 2: Imaging of reporter gene expression in the heart.
Figure 3: PET imaging of cardiac VEGF gene therapy.
Figure 4: Imaging of conditional gene activation in the heart.

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Authors and Affiliations

  1. A Hiona is a Postdoctoral Fellow and JC Wu is an Assistant Professor in the Department of Radiology, and the Department of Medicine, Division of Cardiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA.,

    Asimina Hiona & Joseph C Wu

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  1. Asimina Hiona
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  2. Joseph C Wu
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Correspondence to Joseph C Wu.

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The authors declare no competing financial interests.

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Hiona, A., Wu, J. Noninvasive radionuclide imaging of cardiac gene therapy: progress and potential. Nat Rev Cardiol 5 (Suppl 2), S87–S95 (2008). https://doi.org/10.1038/ncpcardio1113

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