P-Glycoprotein과 Multidrug Resistance Associated Protein을 발현하는 암세포와 종양에서 Tc-99m Sestamibi와 Tc-99m Tetrofosmin의 섭취율 비교 (Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein) |
Author |
조정아.이재태.유정아.서지형.배진호.정신영.안병철.손상균1.하정희2.이규보, |
Jung-Ah Cho, M.D., Jaetae Lee, M.D., Jung Ah Yoo, Ph.D., Ji Hyoung Seo, M.D., Jin Ho Bae, M.D.,Shin Young Jeong, M.D., Byeong Cheol Ahn, M.D., Sang Gyun Sohn, M.D.1, Jeoung-Hee Ha, M.D.2, and Kyubo Lee, M.D. |
Affiliation |
경북대학교 의과대학 핵의학교실, 내과학교실1, 약리학교실2 Department of Nuclear Medicine, Internal Medicine1, and Pharmacology2, School of Medicine, Kyungpook National University, Daegu, Korea |
Abstract |
Purpose: 99mTc-sestamibi(MIBI) and 99mTc-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and
multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors.
To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular
uptakes of 99mTc-MIBI and 99mTc-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant
reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human
colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP
expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry
were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug
concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured
with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated
with or without CsA. Results: RT-PCR, western blot analysis of the cells and immunochemical staining revealed
selective expression of Pgp and MRP for HCT15/CL02 and A549 cells, respectively. There were no significant
difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of
tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and
tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and
6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for
both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240
min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by
the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI
and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating
MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake.
Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in
tumors. (Korean J Nucl Med 39(1):34-43, 2005) |
Keyword |
99mTc-sestamibi, 99mTc-tetrofosmin, Cancer cell, Multidrug resistance, P-glycoprotein, Multidrug resistance associated protein. |
Full text Article |
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