Background: Potassium channel opener (K-opener) opens ATP-sensitive K`-channel located at cell membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip preincubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter TI-201 kinetics in vivo.
Purpose : This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice.
Methods : Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use (5 x 105 cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or 10uM and was co-incubated with TI-201 in HBSS buffer for 20-min to evaluate its effect on cellular Tl-uptake, or challenged to cell preparation pre-incubated with TI-201 for washout study. Two, 40 or 100tig of pinacidil was injected intravenously into ICR mice at 10 min after 51Ci TI-201 injection, and organ uptake and whole body retention rate were measured at different time points.
Results : Co-incubation of pinacidil with T1-201 resulted in a decrease in TI-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced TI-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with 100ig of pinacidil than control.
Conclusion : These results suggest that treatment with K-opener may affect the interpretation of T1-201 myocardial images, due to decreasing thallium accumulation and enhancing washout from myocardium.
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