Evaluation of multidrug resistance in tumors using 99mTc-doxorubicin

Abstract

Doxorubicin (DOX) is a potent chemotherapeutic agent used as the first-choice drug in treating different types of cancer, such as leukemia, lymphoma, and breast cancer, among others. However, the development of multidrug resistance represents a significant obstacle to the successful treatment of tumors. In this study, we assessed whether labeled DOX could be uptaken by susceptible and multidrug-resistant cell lines and by tumors in vivo in animals. The efficiency of DOX labeling was maintained at around 90% in this work. To evaluate the effect of 99mTc-DOX on cells expressing active P-glycoprotein (Pgp), we utilized cultured human chronic myeloid leukemia K562 cells and the resistant counterpart Lucena 1 cells. Lucena 1 cell line showed overexpression of Pgp that was not observed in K562. Our results suggested that the resistance to labeled or unlabeled DOX can be reversed by Pgp inhibition and can be easily detected. In conclusion, administering 99mTc-DOX into mice enables the differentiation between multidrug-resistant tumors in a non-invasive way and the evaluation of tumor resistance and possible chemosensitizers.