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

[C-11]Choline has been established as a PET tracer for imaging prostate cancer. The aim of this study was to determine whether [C-11]choline can be used for monitoring the effects of therapy in a prostate cancer mouse xenograft model. 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 [C-11]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. [C-11]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. The PC-3 tumours could be visualized by [C-11]choline PET. Before treatment the T/M-mean 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 [C-11]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 [C-11]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/M-dyn 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/M-dyn 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. Our results demonstrate that [C-11]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.