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[11C]Choline as pharmacodynamic marker for therapy response assessment in a prostate cancer xenograft model

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[11C]Choline has been established as a PET tracer for imaging prostate cancer. The aim of this study was to determine whether [11C]choline can be used for monitoring the effects of therapy in a prostate cancer mouse xenograft model.

Methods

The androgen-independent human prostate cancer cell line PC-3 was implanted subcutaneously into the flanks of 13 NMRI (nu/nu) mice. All mice were injected 4–6 weeks after xenograft implantation with 37 MBq [11C]choline via a tail vein. Dynamic imaging was performed for 60 min with a small-animal PET/CT scanner (Siemens Medical Solutions). Six mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. Seven mice were treated with PBS as a control. [11C]Choline imaging was performed prior to and 1, 2 and 3 weeks after treatment. To determine choline uptake the images were analysed in terms of tumour-to-muscle (T/M) ratios. Every week the size of the implanted tumour was determined with a sliding calliper.

Results

The PC-3 tumours could be visualized by [11C]choline PET. Before treatment the T/Mmean ratio was 1.6±0.5 in the control group and 1.8±0.4 in the docetaxel-treated group (p=0.65). There was a reduction in the mean [11C]choline uptake after docetaxel treatment as early as 1 week after initiation of therapy (T/M ratio 1.8±0.4 before treatment, 0.9±0.3 after 1 week, 1.1±0.3 after 2 weeks and 0.8±0.2 after 3 weeks). There were no decrease in [11C]choline uptake in the control group following treatment (T/M ratio 1.6±0.5 before treatment, 1.7±0.4 after 1 week, 1.8±0.7 after 2 weeks and 1.7±0.4 after 3 weeks). For analysis of the dynamic data, a generalized estimation equation model revealed a significant decrease in the T/Mdyn ratios 1 week after docetaxel treatment, and the ratio remained at that level through week 3 (mean change −0.93±0.24, p<0.001, after 1  week; −0.78±0.21, p<0.001, after 2 weeks; −1.08±0.26, p<0.001, after 3 weeks). In the control group there was no significant decrease in the T/Mdyn ratios (mean change 0.085±0.39, p=0.83, after 1 week; 0.31±0.48, p=0.52, after 2 weeks; 0.11±0.30, p=0.72, after 3 weeks). Metabolic changes occurred 1 week after therapy and preceded morphological changes of tumour size during therapy.

Conclusion

Our results demonstrate that [11C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a prostate cancer xenograft animal model. The results also indicate that PET with radioactively labelled choline derivatives might be a useful tool for monitoring responses to taxane-based chemotherapy in patients with advanced prostate cancer.

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Acknowledgments

The authors thank Sybille Reder, Elisabeth Aiwanger, Annette Frank and Birgit Pfost for their excellent and extensive technical support.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, , Munich, Germany

    Bernd J. Krause, Michael Souvatzoglou, Ken Herrmann, Axel W. Weber, Andreas K. Buck, Hans-Jürgen Wester, Sibylle I. Ziegler, Reingard Senekowitsch-Schmidtke & Markus Schwaiger

  2. Department of Statistics, Technische Universität München, Munich, Germany

    Tibor Schuster

  3. Institute of Pathology, Technische Universität München, Munich, Germany

    Gregor Weirich

  4. Department of Urology, Technische Universität München, Munich, Germany

    Roman Nawroth & Uwe Treiber

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  1. Bernd J. Krause
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Correspondence to Bernd J. Krause.

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Krause, B.J., Souvatzoglou, M., Herrmann, K. et al. [11C]Choline as pharmacodynamic marker for therapy response assessment in a prostate cancer xenograft model. Eur J Nucl Med Mol Imaging 37, 1861–1868 (2010). https://doi.org/10.1007/s00259-010-1493-2

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  • DOI: https://doi.org/10.1007/s00259-010-1493-2

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