Mechanisms of Tl-201 uptake in a tumor cell line

Mechanisms of uptake of thallium-201 chloride (Tl-201) into cells and intracellular distribution were studied in a cell line of squamous cell carcinoma of adrenal cortex (SW-13). A specified number of cells were incubated with Tl-201 before and after pretreatment with various metabolic and ion-transport inhibitors. Uptake was compared with that of control-one-hour uptake. Nigericin, an ionophore that increases mitochondrial potential but disrupts cell membrane potential, inhibited 57% of uptake. Addition of CCCP after 55 minutes of incubation, an uncoupler of oxidative phosphorylation that decreases mitochondrial potential, did not alter uptake at one hour. Quabain, a cell membrane Na{sup +}K{sup +}ATPase inhibitor, inhibited 65% of uptake with 1 mM dose, however, 55% inhibition was observed with 100 {mu}M dose. Bumetanide, a Na{sup +}K{sup +}2Cl{sup -} cotransport inhibitor, inhibited 36% but no significant inhibition of uptake was observed with dimethyl amiloride (DMA), a Na{sup +}/H{sup +} antiport inhibitor. However, when cells were pretreated with combination of ouabain and bumetanide or ouabain, bumetanide and DMA, there were 86% and 95% inhibition of uptake respectively. Most of the Tl-201 uptake into the cells was due to active transport involving Na{sup +}K{sup +}ATPase system but one-third of its uptake was passive transport involving Na{sup +}K{supmore » +}2Cl{sup -} cotransport and Na{sup +}H{sup +} antiport systems. Intracellular distribution was not related to mitochondria.« less