3′-Deoxy-3′-[18F]fluorothymidine (FLT) uptake in breast cancer cells as a measure of proliferation after doxorubicin and docetaxel treatment

Abstract

The nucleoside analogue [(18)F]fluorothymidine (FLT) has been designed as a marker of cell proliferation that can be imaged in vivo by positron emission tomography. Clinical pilot studies have demonstrated decreasing FLT uptake following antiproliferative chemotherapy of breast cancer. However, the significance of posttreatment FLT uptake has not been evaluated at the cell level. The aim of this study was to investigate whether FLT uptake detects proliferation inhibition induced by docetaxel or doxorubicin treatment in an in vitro breast cancer model. Breast cancer cells (MCF-7) were treated with docetaxel or doxorubicin for 24 h at drug doses inducing 25-99% inhibition of clonogenic survival (IC(25) to IC(99)). Cellular FLT uptake was estimated at 4 h and at 1, 3 and 5 days interval from chemotherapy. [(3)H]Thymidine incorporation and S-phase fraction were measured for comparison. Analysis of variance and the Bland-Altman difference plot were employed for statistical analysis. After treatment, FLT uptake was declined in dependence of the proliferation inhibition mediated by both chemotherapeutic agents (all P<.0001). The decrease of FLT was greater after doxorubicin treatment than after the corresponding docetaxel dose. With doxorubicin (IC(99)), FLT accumulation was reduced by 70% as early as 4 h after treatment. FLT uptake was closely correlated to [(3)H]thymidine incorporation and S-phase fraction (r=.84 to .93). Right after docetaxel or doxorubicin treatment, FLT uptake corresponds to the reduction of tumor cell proliferation induced. [(18)F]FLT appears promising for monitoring chemosensitivity in breast cancer.