MRP발현 인체 비소세포 폐암 A549에서 Tc-99m MIBI와 Tc-99m Tetrofosmin섭취의 비교 (Comparison of the Uptakes of Tc-99m MIBI and Tc-99m Tetrofosmin in A549, an MRP-expressing Cancer Cell, In Vitro and In Vivo) |
Author |
유정아, 정신영, 서명랑, 배진호, 안병철, 이규보, 최상운, 이병호, 이재태, |
Jeong Ah Yoo, Ph.D., Shin Young Jeong, M.D., Myung Rang Seo, B.S., Jin Ho Bae, M.D.,Byeong Cheol Ahn, M.D., Kyu Bo Lee, M.D., Sang Woon Choi, Ph.D., Byung Ho Lee,Ph.D., Jaetae Lee, M.D. |
Affiliation |
경북대학교 의과대학 핵의학교실, 한국화학연구소 Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, Bioorganic Science Division,1 Korea Institute of Chemical Technology, Daejeon, Korea |
Abstract |
Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell
lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro
and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for
detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated
at 100 μM of verapamil (Vrp), 50 μM of cyclosporin A (CsA) and 25 μM of butoxysulfoximide (BSO) after
incubation with MIBI and tetrofosmin for 30 and 60 min at 37℃, using single cell suspensions at 1×106
cells/ml. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells
were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI
or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of
370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and
tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot
analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of
tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549
cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin.
Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage
increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629%
and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI
and tetrofosmin between Gr1 and Gr3. Percentage increases in 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 higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and
tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be
a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators. |
Keyword |
Tc-99m MIBI, Tc-99m Tetrofosmin, Verapamil, Cyclosporin A, Butoxysulfoximide, Multidrug |
Full text Article |
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