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

• Published in: Journal of the American College of Cardiology Vol. 52; no. 20; pp. 1652 - 1660
• Main Authors: Terrovitis, John, Kwok, Keng Fai, Lautamäki, Riikka, Engles, James M., Barth, Andreas S., Kizana, Eddy, Miake, Junichiro, Leppo, Michelle K., Fox, James, Seidel, Jurgen, Pomper, Martin, Wahl, Richard L., Tsui, Benjamin, Bengel, Frank, Marbán, Eduardo, Abraham, M. Roselle
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.11.2008; Elsevier Limited
• Subjects: Adult Stem Cells - transplantation; Animals; Cardiology; 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; stem cells; CDC; rCDC; MRI; LV; imaging; CMV; SPECT; CR; CT; RT-PCR; NIS; PET; computed tomography; magnetic resonance imaging; sodium-iodide symporter; reverse transcription-polymerase chain reaction; cardiac-derived stem cell; rat cardiac-derived stem cell; cytomegalovirus promoter; contrast ratio; left ventricle/ventricular; positron emission tomography; single-photon emission computed tomography
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2008.06.051

We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m (99mTc) or iodine 124 (124I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo. 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 99mTc (or 124I) 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. NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring 99mTc uptake. NIS+ rCDCs were visualized in vivo as regions of 99mTc or 124I 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 99mTc signals were localized to the cell injection sites. 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.