Author |
이재태(Jae Tae Lee),김은지(Eun Ji Kim),안병철(Byeong Cheol Ahn),손상균(Kang Kyun Sohn),이규보(Kyu Bo Lee),하정희(Jeoung Hee Ha),김천기(Chun K . Kim), |
Abstract |
Background: Potassium channel opener (K-opener) opens
ATP-sensitive K+-channel located at 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-vive 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 biodi- stribution 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 (5×105 cells/ml). Pinacidil was dissolved in 10%
DMSO solution at a final concentration of 100nM or 10uM
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 100μg of pinacidil
was injected intravenously into ICR mice at 10 min
after 5μCi 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 100μg of pinacidil than control.
Conclusion: These results suggest that treatment with
K-opener may affect the interpretation of T1-
201myocardial images, due to decreasing thallium
accumulation and enhancing washout from myocardium. |