Tracers to Monitor the Response to Chemotherapy: <I>In Vitro</I> Screening of Four Radiopharmaceuticals

Abstract

Objectives: It has been postulated that radiopharmaceuticals can be used to predict the therapeutic response to (chemo)therapy, which could lead to individualized treatment regimens. In this study, and 125 I-methyltyrosine were tested for this purpose. Methods: The uterine sarcoma cell line MES-SA (MDRϪ) and its multidrug resistant variant, MES-SA/Dx5 (MDRϩ), were used. The MDRϩ cells express high levels of P-glycoprotein, which makes them relatively resistant to various chemotherapeutic agents. Cells were cultured in the presence of escalating concentrations of doxorubicin, and the cellular uptake of the radiopharmaceuticals was determined. Results: Decreasing 18 F-deoxyglucose uptake at escalating doxorubicin concentrations reflected the chemosensitivity of the cells: 18 F-deoxyglucose uptake in the MDRϪ cells was reduced to 40% of the baseline level in the presence of 1 M of doxorubicin, compared to 74% in the MDRϩ cells. The 125 Ideoxyuridineribose uptake in MDRϪ cells was reduced to 2% of the baseline level when cultured at a concentration of 1 M of doxorubicin, while this was 79% in the MDRϩ cells. The same trend was observed with 125 I-methyltyrosine. The enhanced doxorubicin chemosensitivity of MDRϩ cells in the presence of verapamil, a modulator of P-glycoprotein, was reflected by the reduced uptake of 18 F-deoxyglucose, 125 I-deoxyuridineribose, and 125 I-methyltyrosine. Furthermore, baseline 99m Tc-tetrofosmin uptake in MDRϩ cells was more than six-fold lower than in MDRϪ cells. Conclusion: In the presence of doxorubicin, the uptake of 18 F-deoxyglucose, 125 I-deoxyuridineribose and, to a lesser extent, 125 I-methyltyrosine is more pronouncedly reduced in MDRϪ cells than in MDRϩ cells. The reversal of doxorubicin-resistance of MDRϩ cells by verapamil was also reflected by the uptake of 18 F-deoxyglucose, 125 I-deoxyuridineribose, and 125 I-methyltyrosine. 99m Tc-tetrofosmin uptake reflected P-glycoprotein expression without exposure to doxorubicin.