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

Dittmann, Helmut; Jusufoska, Ajnur; Dohmen, Bernhard Matthias; Smyczek-Gargya, Brigitte; Fersis, Nikos; Pritzkow, Maren; Kehlbach, Rainer; Vonthein, Reinhard; Machulla, Hans Juergen; Bares, Roland

doi:10.1016/j.nucmedbio.2008.10.012

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 2 , Pages 163-169, February 2009

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

Helmut Dittmann
- Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
- Corresponding author. Department of Nuclear Medicine, University of Tuebingen, Otfried-Mueller-Str. 14, D-72076 Tuebingen, Germany. Tel.: +49 7071 29 82179; fax: +49 7071 29 5869.
Ajnur Jusufoska
- Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
Bernhard Matthias Dohmen
- Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
Brigitte Smyczek-Gargya
- Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
Nikos Fersis
- Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
Maren Pritzkow
- Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
Rainer Kehlbach
- Department of Diagnostic Radiology, Eberhard-Karls-University, Tuebingen D-72076, Germany
Reinhard Vonthein
- Department of Medical Biometry, Eberhard-Karls-University, Tuebingen D-72076, Germany
Hans Juergen Machulla
- Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
Roland Bares
- Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany

Received 10 October 2008; accepted 25 October 2008.

Abstract

Introduction

The nucleoside analogue [¹⁸F]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.

Methods

Breast cancer cells (MCF-7) were treated with docetaxel or doxorubicin for 24 h at drug doses inducing 25–99% inhibition of clonogenic survival (IC₂₅ to IC₉₉). Cellular FLT uptake was estimated at 4 h and at 1, 3 and 5 days interval from chemotherapy. [³H]Thymidine incorporation and S-phase fraction were measured for comparison. Analysis of variance and the Bland–Altman difference plot were employed for statistical analysis.

Results

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 (IC₉₉), FLT accumulation was reduced by 70% as early as 4 h after treatment. FLT uptake was closely correlated to [³H]thymidine incorporation and S-phase fraction (r=.84 to .93).

Conclusions

Right after docetaxel or doxorubicin treatment, FLT uptake corresponds to the reduction of tumor cell proliferation induced. [¹⁸F]FLT appears promising for monitoring chemosensitivity in breast cancer.

Keywords: Positron emission tomography, Fluorothymidine, Breast cancer, Doxorubicin, Docetaxel