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.
OBJECTIVE
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, using (99m)Tc (or (124)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 measuring (99m)Tc uptake. NIS(+) rCDCs were visualized in vivo as regions of (99m)Tc or (124)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 vivo (99m)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.
Terrovitis
John
J
Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.
Kwok
Keng Fai
KF
Lautamäki
Riikka
R
Engles
James M
JM
Barth
Andreas S
AS
Kizana
Eddy
E
Miake
Junichiro
J
Leppo
Michelle K
MK
Fox
James
J
Seidel
Jurgen
J
Pomper
Martin
M
Wahl
Richard L
RL
Tsui
Benjamin
B
Bengel
Frank
F
Marbán
Eduardo
E
Abraham
M Roselle
MR
D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters