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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.
J Am Coll Cardiol 2008; 52(20):1652-60JACC

Abstract

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, 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.

Authors+Show Affiliations

Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18992656

Citation

Terrovitis, John, et al. "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." Journal of the American College of Cardiology, vol. 52, no. 20, 2008, pp. 1652-60.
Terrovitis J, Kwok KF, Lautamäki R, et al. 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. J Am Coll Cardiol. 2008;52(20):1652-60.
Terrovitis, J., Kwok, K. F., Lautamäki, R., Engles, J. M., Barth, A. S., Kizana, E., ... Abraham, M. R. (2008). 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. Journal of the American College of Cardiology, 52(20), pp. 1652-60. doi:10.1016/j.jacc.2008.06.051.
Terrovitis J, et al. 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. J Am Coll Cardiol. 2008 Nov 11;52(20):1652-60. PubMed PMID: 18992656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Terrovitis,John, AU - Kwok,Keng Fai, AU - Lautamäki,Riikka, AU - Engles,James M, AU - Barth,Andreas S, AU - Kizana,Eddy, AU - Miake,Junichiro, AU - Leppo,Michelle K, AU - Fox,James, AU - Seidel,Jurgen, AU - Pomper,Martin, AU - Wahl,Richard L, AU - Tsui,Benjamin, AU - Bengel,Frank, AU - Marbán,Eduardo, AU - Abraham,M Roselle, PY - 2008/02/26/received PY - 2008/05/07/revised PY - 2008/06/19/accepted PY - 2008/11/11/pubmed PY - 2008/12/17/medline PY - 2008/11/11/entrez SP - 1652 EP - 60 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 52 IS - 20 N2 - 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, 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. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/18992656/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(08)02880-5 DB - PRIME DP - Unbound Medicine ER -