technetium-tc-99m-tetrofosmin and 5-dimethylamiloride

The mechanisms of uptake and intracellular distribution of 99mTc-tetrofosmin, 99mTc-MIBI and 201TI and the behaviors of 99mTc-tetrofosmin and 99mTc-MIBI in relation to Na+ were studied with primary cultures of myocardial cells.. Both the uptake and the washout of the tracers were sequentially measured. The cells were treated with ouabain, bumetanide, tetrodotoxin, dimethyl amiloride (DMA), nigericin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) to observe the effects of the uptake and intracellular distribution of the traders. Cells equilibrated in buffers with or without Na+ were treated with monensin and DMA to evaluate the effect of Na+ on the accumulation of the tracers.. Despite the similarities in uptake kinetics, there was a higher level of retention of 99mTc-tetrofosmin inside the cells. Ouabain, bumetanide and tetrodotoxin did not show any inhibitory effect on the uptake of 99mTc-tetrofosmin and 99mTc-MIBI, whereas they produced various degrees of inhibition of 201TI uptake. DMA produced approximately 35% inhibition of 99mTc-tetrofosmin uptake and 50% inhibition of 99mTc-MIBI uptake. Nigericin increased the uptake of 99mTc-MIBI by the cells. The addition of CCCP produced the release of 38% of the accumulated 99mTc-tetrofosmin and 52%-70% of the accumulated 99mTc-MIBI, indicating that these percentages of accumulation were related to mitochondrial uptake. Neither Na+-free buffer nor monensin had any significant effect on 99mTc-tetrofosmin accumulation, but they both caused increased accumulation of 99mTc-MIBI.. The uptake of both 99mTc-tetrofosmin and 99mTc-MIBI through the cell membrane is partly related to the Na+/H+ antiporter system. Only part of the accumulated 99mTc-tetrofosmin inside the cells enters into mitochondria; most of the accumulated 99mc-MIBI is related to mitochondrial uptake. This uptake may be related to Na+.

Topics: Amiloride; Animals; Bumetanide; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cell Survival; Cells, Cultured; Heart; Ion Transport; Membrane Potentials; Mitochondria, Heart; Monensin; Myocardium; Nigericin; Organophosphorus Compounds; Organotechnetium Compounds; Ouabain; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Sodium; Technetium Tc 99m Sestamibi; Tetrodotoxin; Thallium Radioisotopes

The kinetics, intracellular distribution and effects of ion transport inhibitors on the uptake of 99Tcm-tetrofosmin, 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) and 201Tl were investigated in a tumour cell line. Both uptake and washout of the tracers were measured at specific intervals. Cells were treated with ouabain, dimethyl amiloride (DMA) and bumetanide to observe the effects on uptake, while carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used to study the release of the tracers. The tracers showed similar uptake and washout kinetics. Ouabain inhibited 55-67% of 201Tl, 16-22% of 99Tcm-tetrofosmin and 8-14% of 99Tcm-MIBI. DMA inhibited the uptake of both 99Tcm-tetrofosmin (30%) and 99Tcm-MIBI (21%). Bumetanide stimulated the uptake of 99Tcm-tetrofosmin and 99Tcm-MIBI but inhibited that of 201Tl (37%). When cells were pretreated with various combinations of these ion transport inhibitors, the uptake of 201Tl was related to Na+,K+ pump, Na+,K+, 2Cl- co-transport systems, whereas the uptake of both 99Tcm-tetrofosmin and 99Tcm-MIBI was related to the Na+,K+ pump, Na+/H+ antiport systems. Addition of CCCP released 55% and 90% of accumulated 99Tcm-tetrofosmin and 99Tcm-MIBI respectively, indicating that the percentage released was related to mitochondrial uptake.

Topics: Amiloride; Biological Transport; Bumetanide; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carrier Proteins; Contrast Media; Humans; Kinetics; Organophosphorus Compounds; Organotechnetium Compounds; Ouabain; Potassium; Sodium; Sodium-Hydrogen Exchangers; Sodium-Potassium-Chloride Symporters; Sodium-Potassium-Exchanging ATPase; Technetium Tc 99m Sestamibi; Thallium Radioisotopes; Tumor Cells, Cultured