Abstract
The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET α-emitter astatine-211 (211At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 (123I), 340-fold for technetium-99m pertechnetate (99mTcO4 –) and 60-fold for 211At. Cellular 211At accumulation was found to be dependent on extracellular Na+ ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and 99mTcO4 – uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated 211At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and 211At were rapidly (apparent t 1/2 3–15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times (123I), 25 times (99mTcO4 –) and 10 times (211At) higher than in control tumours or normal tissues except stomach (3–5 times) and thyroid gland (5–10 times). Thirty-four percent and 14% of the administered activity of 123I and 211At, respectively, was found in NIS tumours by region of interest analysis (n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for 123I, 5.2 h for 211At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBqtumour for 131I and 50.3 Gy/MBqtumour for 211At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy α-emitter 211At is efficiently transported by NIS. Application of 211At may direct higher radiation doses to experimental tumours than those calculated for 131I. Thus, 211At may represent a promising alternative radionuclide for future NIS-based tumour therapy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Author information
Authors and Affiliations
Additional information
Received 20 October 2001 and in revised form 28 January 2002
Electronic Publication
Rights and permissions
About this article
Cite this article
Petrich, T., Helmeke, HJ., Meyer, G. et al. Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter. Eur J Nucl Med 29, 842–854 (2002). https://doi.org/10.1007/s00259-002-0784-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-002-0784-7