Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter

• Published in: Biochemical and biophysical research communications Vol. 325; no. 1; pp. 157 - 166
• Main Authors: Dingli, David, Bergert, Elizabeth R., Bajzer, Željko, O'Connor, Michael K., Russell, Stephen J., Morris, John C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.12.2004
• Subjects: Animals; Female; Gene theraphy; Humans; Iodides - pharmacokinetics; Iodine Radioisotopes - pharmacokinetics; Isotopes; K562 Cells; Mechanisms; Mice; Mice, SCID; Neoplasm Transplantation; Neoplasms - metabolism; Neoplasms - pathology; Perchlorates - pharmacokinetics; Rats; Sodium iodide symporter; Symporters - pharmacokinetics; Sodium iodide symporter; Mechanisms; Gene theraphy; Isotopes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.09.219

The thyroidal sodium iodide symporter (NIS) in combination with various radioactive isotopes has shown promise as a therapeutic gene in various tumor models. Therapy depends on adequate retention of the isotope in the tumor. We hypothesized that in the absence of iodide organification, isotope trapping is a dynamic process either due to slow efflux or re-uptake of the isotope by cells expressing NIS. Iodide efflux is slower in ARH-77 and K-562 cells expressing NIS compared to a thyroid cell line. Isotope retention half times varied linearly with the number of cells expressing NIS. With sufficient NIS expression, iodide efflux is a zero-order process. Efflux kinetics in the presence or absence of perchlorate also supports the hypothesis that iodide re-uptake occurs and contributes to the retention of the isotope in tumor cells. Iodide organification was insignificant. In vivo studies in tumors composed of mixed cell populations confirmed these observations.