Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;2(4):392-402.
doi: 10.7150/thno.3722. Epub 2012 Apr 11.

Sodium iodide symporter for nuclear molecular imaging and gene therapy: from bedside to bench and back

Byeong-Cheol Ahn  1
Affiliations

Sodium iodide symporter for nuclear molecular imaging and gene therapy: from bedside to bench and back

Byeong-Cheol Ahn. Theranostics. 2012.

Abstract

Molecular imaging, defined as the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms, can be obtained by various imaging technologies, including nuclear imaging methods. Imaging of normal thyroid tissue and differentiated thyroid cancer, and treatment of thyroid cancer with radioiodine rely on the expression of the sodium iodide symporter (NIS) in these cells. NIS is an intrinsic membrane protein with 13 transmembrane domains and it takes up iodide into the cytosol from the extracellular fluid. By transferring NIS function to various cells via gene transfer, the cells can be visualized with gamma or positron emitting radioisotopes such as Tc-99m, I-123, I-131, I-124 and F-18 tetrafluoroborate, which are accumulated by NIS. They can also be treated with beta- or alpha-emitting radionuclides, such as I-131, Re-186, Re-188 and At-211, which are also accumulated by NIS. This article demonstrates the diagnostic and therapeutic applications of NIS as a radionuclide-based reporter gene for trafficking cells and a therapeutic gene for treating cancers.

Keywords: gene therapy; molecular imaging; radionuclide-based imaging; radionuclide.; sodium iodide symporter.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Iodide uptake function of NIS. NIS transports 2 sodium ions and 1 iodide ion into the cytoplasm together. The electrochemical sodium gradient generated by the oubaine-sensitive Na+/K+ ATPase pump provides energy for this transfer.
Figure 2
Figure 2
A 21-year-old female who underwent total thyroidectomy due to papillary thyroid cancer. Chest simple radiography and CT did not demonstrate any metastatic lesion of the cancer in the neck and chest regions. However, a radioiodine whole body scan revealed lymph node metastases (white arrow) in the right supraclavicular area and diffuse lung metastases (black arrows).
Figure 3
Figure 3
Cells without NIS gene expression obtain the function of iodine uptake with NIS gene transduction by viral or non-viral vector delivery. The cells can be imaged by radionuclide-based molecular imaging techniques using gamma ray or positron-emitting radiotracers and be cleared by beta or alpha particle-emitting radionuclides.
Figure 4
Figure 4
Visualization of macrophages expressing NIS with radionuclide-based molecular imaging. Inflammation at the right thigh (yellow arrow) was well visualized in F-18 FDG microPET imaging. Migration of microphages expressing NIS to the inflammation site (white arrow) was clearly visualized on I-124 microPET imaging .
Figure 5
Figure 5
Visualization of tumor cells expressing NIS with optical molecular imaging using I-124. Tumor xenografts of anaplastic thyroid cancer cells expressing NIS were well visualized on both microPET imaging (white arrows) and Cerenkov luminescence imaging (black arrows) after intravenous administration of I-124 .
Figure 6
Figure 6
A 26-year-old female who underwent total thyroidectomy due to papillary thyroid cancer. (A) Chest simple radiograph did not demonstrate any observable metastatic lesions of the cancer. (B) CT scan of the chest demonstrated several metastatic lesions of the cancer in both lung fields (white arrows). TSH-stimulated serum thyroglobulin was 65.0 ng/mL. The patient was diagnosed with metastatic thyroid cancer of the lung. (C) A post initial high dose I-131 treatment (150 mCi) scan revealed numerous metastatic lung lesions. (D) A post 2nd high dose I-131 treatment (200 mCi) scan revealed fewer but still several metastatic lung lesions (black arrows). (E, F) A post 3rd high dose I-131 treatment (200 mCi) scan revealed no remarkable radioiodine uptake in both lung fields and chest CT showed only tiny lung nodules having no clinical significance. TSH-stimulated serum thyroglobulin was 1.4 ng/mL after the third treatment. The patient had achieved complete remission with three times of high dose I-131 treatment and her status still remains disease-free at 7 years follow-up.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Riesco-Eizaguirre G, Santisteban P. A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol. 2006;155:495–512. - PubMed
    1. Soto GD, Halperin I, Squarcia M, Lomena F, Domingo MP. Update in thyroid imaging. The expanding world of thyroid imaging and its translation to clinical practice. Hormones (Athens) 2010;9:287–98. - PubMed
    1. Verburg FA, de Keizer B, van Isselt JW. Use of radiopharmaceuticals for diagnosis, treatment, and follow-up of differentiated thyroid carcinoma. Anticancer Agents Med Chem. 2007;7:399–409. - PubMed
    1. Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 1996;379:458–60. - PubMed
    1. Msaouel P, Dispenzieri A, Galanis E. Clinical testing of engineered oncolytic measles virus strains in the treatment of cancer: an overview. Curr Opin Mol Ther. 2009;11:43–53. - PMC - PubMed