Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 52, Issue 20, Pages 1652-1660Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2008.06.051
Keywords
stem cells; imaging; SPECT; PET
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Funding
- NCI NIH HHS [U24 CA92871] Funding Source: Medline
- NHLBI NIH HHS [R01 HL092985] Funding Source: Medline
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Objectives We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m (Tc-99m) or iodine 124 (I-124), 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, using Tc-99m ( or I-124) 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 measuring Tc-99m uptake. NIS+ rCDCs were visualized in vivo as regions of Tc-99m or I-124 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 vivo Tc-99m 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. (J Am Coll Cardiol 2008; 52: 1652-60) (c) 2008 by the American College of Cardiology Foundation
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