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Title:

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

Document type:
Journal Article
Author(s):
Krause, BJ; Souvatzoglou, M; Herrmann, K; Weber, AW; Schuster, T; Buck, AK; Nawroth, R; Weirich, G; Treiber, U; Wester, HJ; Ziegler, SI; Senekowitsch-Schmidtke, R; Schwaiger, M
Abstract:
PURPOSE: [(11)C]Choline has been established as a PET tracer for imaging prostate cancer. The aim of this study was to determine whether [(11)C]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 [(11)C]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. [(11)C]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 [(11)C]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 [(11)C]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 [(11)C]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. CONCLUSION: Our results demonstrate that [(11)C]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.
Journal title abbreviation:
Eur J Nucl Med Mol Imaging
Year:
2010
Journal volume:
37
Journal issue:
10
Pages contribution:
1861-8
Language:
eng
Fulltext / DOI:
doi:10.1007/s00259-010-1493-2
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/20512572
Print-ISSN:
1619-7070
TUM Institution:
Institut für Allgemeine Pathologie und Pathologische Anatomie; Institut für Medizinische Statistik und Epidemiologie; Klinik und Poliklinik für Nuklearmedizin; Urologische Klinik und Poliklinik
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