Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein / 대한핵의학회잡지

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.

Scintigraphic Evaluation of Hematologic Diseases with Tc-99m Labeled Antigranulocyte Antibody / 대한혈액학회지

BACKGROUND: Bone marrow scintigraphy using Tc-99m labeled antigranulocyte antibody has been reported to be able to evaluate bone marrow status. We have performed antigranulocyte antibody scan and hematopoietic activity in order to identify bone marrow status in patients with hematologic diseases. METHODS: Sixty-nine patients were enrolled in this study from October 1995 to May 1997. Images were acquired at four and twenty-four hour after injecion of 20mCi 99mTc labeled antigranulocyte antibody (BW 250/183). Patients were divided into four groups according to scintigraphic findings, those with increased marrow uptake (marrow expansion), decreased uptake, focal defect and normal findings. RESULTS: Leukemias and myelodysplastic syndromes frequently showed bone marrow expansion. Seventeen of 21 patients (81%) with AML, and all of ALL and biphenotypic leukemias showed bone marrow expansion. Five of 6 with CML, all Hodgkin's diseases and 3 of 4 MDS also showed marrow expansion. In contrast, all aplastic anemia patients showed decreased marrow uptake, and extra-axial noted in 2 patients with aplastic anemia. All of ten patients with multiple myeloma and 2 of 4 (50%) with Hodgkin disease showed focal marrow defects. Three of 11 with non-Hodgkin lymphoma and 4 of 21 with AML also showed focal marrow defects. CONCLUSION: Bone marrow scintigraphy using antigranulocyte antibody has clearly demonstrated the distribution of bone marrow in various hematologic diseases. Thus, it seems to be a useful method in the assessment of bone marrow status in patients with hematologic disease.