Effects of Potassium-Channel Opener on Thallium-201 Kinetics: In-vitro Study in Rat Myocyte Preparations and In-vivo Mice Biodistribution Study

K-통로개방제가 배양심근세포와 생쥐 체내의 Thallium-201역동학에 미치는 영향

  • Lee, Jae-Tae (Department of Nuclear Medicine, School of Medicine, Kyungpook Ntional University) ;
  • Kim, Eun-Ji (Department of Nuclear Medicine, School of Medicine, Kyungpook Ntional University) ;
  • Ahn, Byeong-Cheol (Department of Nuclear Medicine, School of Medicine, Kyungpook Ntional University) ;
  • Sohn, Kang-Kyun (Department of Nuclear Medicine, School of Medicine, Kyungpook Ntional University) ;
  • Lee, Kyu-Bo (Department of Nuclear Medicine, School of Medicine, Kyungpook Ntional University) ;
  • Ha, Jeoung-Hee (Department of Pharmacology, Youngnam University Medical School) ;
  • Kim, Chun-K. (Mt. Sinai School of Medicine, New York)
  • Published : 1996.12.20

Abstract

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 pre-incubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 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 ($5{\times}10^5$ cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or l0uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or $100{\mu}g$ of pinacidil was injected intravenously into ICR mice at 10 min after $5{\mu}Ci$ T1-201 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 T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 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 $100{\mu}g$ 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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