[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]

Nuklearmedizin. 2013;52(4):141-7. doi: 10.3413/Nukmed-0521-12-07. Epub 2013 Feb 11.
[Article in German]

Abstract

The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT.

Animals, methods: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio).

Results: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group.

Conclusion: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carbon Radioisotopes / pharmacokinetics
  • Cell Line, Tumor
  • Choline / pharmacokinetics*
  • Docetaxel
  • Male
  • Mice
  • Mice, SCID
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Taxoids
  • Docetaxel
  • Choline