Dynamic iodide trapping by tumor cells expressing the thyroidal sodium iodide symporter.
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.
Dingli
David
D
Molecular Medicine Program, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Bergert
Elizabeth R
ER
Bajzer
Zeljko
Z
O'connor
Michael K
MK
Russell
Stephen J
SJ
Morris
John C
JC
D000818:Animals; D005260:Female; D006801:Humans; D007454:Iodides / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D020014:K562 Cells; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010472:Perchlorates / Q000493:pharmacokinetics; D051381:Rats; D027981:Symporters / Q000493:pharmacokinetics*; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D007457:Iodine Radioisotopes; D010472:Perchlorates; D027981:Symporters; D000099209:Sodium-Iodide Symporters