Effect of Multidrug Resistance Gene-1 (mdr1) Overexpression on In-Vitro Uptake of 99mTc-sestaMIBI in Murine L1210 Leukemia Cells

Chun, Kyung Ah; Lee, Jaetae; Lee, Sang Woo; Kang, Do Young; Sohn, Sang Kyun; Lee, Jong Kee; Chung, June Key; Jun, Soo Han; Lee, Kyu Bo

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.