Effect of Multidrug Resistance Gene-1 (mdr1) Overexpression on In-Vitro Uptake of 99mTc-sestaMIBI in Murine L1210 Leukemia Cells.
- Author:
Kyu Bo LEE
;
June Key CHUNG
;
Sang Kyun SOHN
;
Kyung Ah CHUN
;
Do Young KANG
;
Sang Woo LEE
;
Jaetae LEE
;
Jong Kee LEE
;
Soo Han JUN
- Publication Type:In Vitro ; Original Article
- Keywords:
Multidrug resistance;
MDR-reversing agent
- MeSH:
Animals;
Cell Line;
Cyclosporine;
Dipyridamole;
Doxorubicin;
Drug Resistance, Multiple*;
Leukemia L1210;
Leukemia*;
P-Glycoprotein;
Technetium Tc 99m Sestamibi*;
Verapamil;
Vincristine
- From:Korean Journal of Nuclear Medicine
1999;33(2):152-162
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: To determine whether Tc-99mMIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively Tc-99mMIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular Tc-99m-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. MATERIALS AND METHODS: We measured percentage uptake of Tc-99m-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of Tc-99m-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. RESULTS: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of Tc-99m-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 degree C than 4 degree C. In the presence of verapamil, cyclosporin or dipyridamole, Tc-99m-MIBI uptake was increased upto 604% in mdr1 positive cells. CONCLUSION: Cellular uptake of Tc-99m-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest that Tc-99m-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents In vitro.
