• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

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 $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. 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.

• Journal of the Korean earth science society
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• v.21 no.4
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• pp.449-468
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• 2000

The Ordovician Chongson Limestone deposited in the carbonate ramp to the rimmed shelf shows diverse diagenetic features. The marine diagenetic feature appears as isopachous cements surrounding ooids and peloids. Meteoric diagenetic features are recrystallized finely and coarsely crystalline calcite, evaporite casts filled with calcite, and isopachous sparry calcite surrounding ooid grains. Shallow burial diagenetic features include wispy seam, microstylolite, and dissolution seam whereas deep burial features include stylolite, burial cements. blocky calcite with twin lamellae, and poikilotopic calcite. Dolomites consist of very finely to finely crystalline mosaic dolomite formed as supratidal dolomite, disseminated dolomite of diverse origin, patchy dolomite formed from bioturbated mottles, and saddle dolomite of burial origin. Silicified features include calcite-replacing quartz and fracture-filling megaquartz. Burial cements characterized by poikilotopic texture show ${\delta}^{18}$O value of -10.4 %$_o$ PDB, ${\delta}^{13}$C value of -1.0%$_o$ PDB and 504ppm Sr, 3643ppm Fe, and 152ppm Mn concentrations. Finely and coarsely crystalline limestones show similar ${\delta}^{18}$O and ${\delta}^{13}$C value to those of burial cements; however, they show lower Sr and higher Fe and Mn concentrations than burial cements. This suggests that very finely and coarsely crystalline limestones were recrystallized in freshwater and then they were readjusted geochemically in the burial setting whereas the burial cements were formed in relatively high temperature and low water/rock ratio conditions. Very finely and finely crystalline mosaic dolomites with ${\delta}^{18}$O value of -8.2%$_o$ PDB, ${\delta}^{13}$C value of -1.9 %$_o$ PDB, and 213ppm Sr, 3654ppm Fe, and 114ppm Mn concentrations, respectively are interpreted to have been formed penecontemporaneously in supratidal flat and then recrystallized in the low water/rock ratio burial environment. Geochemical data suggest that the low water/rock ratio burial environment was the dominant diagenetic setting in the Chongson Limestone. The Chongson Limestone has experienced marine and meteoric diagenesis during early diagenesis. With deposition of Haengmae and Hoedongri formations part of the Chongson Limestone was buried beneath these formations and it experienced shallow burial diagenesis. During the Devonian the Chongson Limestone was tectonically deformed and subaerially exposed. During the Carboniferous to the Permian about 3.3km thick Pyongan Supergroup was deposited on the Chongson Limestone and the Chongson Limestone was in deep burial depths and stylolite, burial cements, blocky calcite and saddle dolomite were formed. After this burial event the Chongson Limestone was subaerially exposed during the Mesozoic and Cenozoic by three periods of tectonic disturbance including Songnim, Daebo and Bulguksa disturbance. Since the Bulguksa disturbance during Cretaceous and early Tertiary the Chongson Limestone has been subaerially exposed.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-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 $^{99m}Tc$-MIBI and $^{99m}Tc$-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 irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/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.