Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography

Objectives We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m (99m Tc) or iodine 124 (124 I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Background Stem...

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Published in:	Journal of the American College of Cardiology 2008-11, Vol.52 (20), p.1652-1660
Main Authors:	Terrovitis, John, MD, Kwok, Keng Fai, BS, Lautamäki, Riikka, MD, PhD, Engles, James M., MS, MBA, Barth, Andreas S., MD, PhD, Kizana, Eddy, MBBS, PhD, Miake, Junichiro, MD, PhD, Leppo, Michelle K., BS, Fox, James, BS, Seidel, Jurgen, PhD, Pomper, Martin, MD, PhD, Wahl, Richard L., MD, Tsui, Benjamin, PhD, Bengel, Frank, MD, Marbán, Eduardo, MD, PhD, Abraham, M. Roselle, MD
Format:	Article
Language:	eng
Subjects:	Adult Stem Cells - transplantation Animals Cardiovascular Cell Survival Cells, Cultured Cytomegalovirus Gamma rays Genes, Reporter Heart Heart attacks Humans imaging Immunohistochemistry Internal Medicine Iodine Radioisotopes Methods Myocardium - cytology Myocardium - metabolism PET Positron-Emission Tomography Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Sodium Sodium Pertechnetate Tc 99m SPECT Stem cells Studies Symporters - genetics Symporters - metabolism Tomography, Emission-Computed, Single-Photon
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Summary:	Objectives We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m (99m Tc) or iodine 124 (124 I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Background Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo. Methods The human NIS complementary deoxyribonucleic acid was transduced into rat cardiac-derived stem cells (rCDCs) using lentiviral vectors. Rats were injected intramyocardially with up to 4 million NIS+ -rCDCs immediately after left anterior descending coronary artery ligation. Dual isotope SPECT (or PET) imaging was performed, using99m Tc (or124 I) for cell detection and thallium 201 (or ammonia 13) for myocardial delineation. In a subset of animals, high resolution ex vivo SPECT scans of explanted hearts were obtained to confirm that in vivo signals were derived from the cell injection site. Results NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring99m Tc uptake. NIS+ rCDCs were visualized in vivo as regions of99m Tc or124 I uptake within a perfusion deficit in the SPECT and PET images, respectively. Cells could be visualized by SPECT up to 6 days post-injection. Ex vivo SPECT confirmed that in vivo99m Tc signals were localized to the cell injection sites. Conclusions Ectopic NIS expression allows noninvasive in vivo stem cell tracking in the myocardium, using either SPECT or PET. The general approach shows significant promise in tracking the fate of transplanted cells participating in cardiac regeneration, given its ability to observe living cells using clinically applicable imaging modalities.
ISSN:	0735-1097 1558-3597