Ansprechen auf eine Docetaxel-therapie im LNCaP-Prostata-karzinom-Xenograft-Mausmodell

Summary

The aim of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaPprostate 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.

Zusammenfassung

Ziel: Untersuchung des Ansprechens auf eine Docetaxeltherapie in einem LNCaP-Prostatakarzinom-Xenograft-Mausmodell mit der [¹¹C]Cholin-Kleintier-PET/CT. Tiere, Methoden: Die androgenabhängige humane Prostatakarzinomzelllinie LNCaP wurde subkutan in die linke Flanke von 17 SCID-Mäusen implantiert und 12.5 mg Testosteronplättchen wurden in die Nackenfalte eingebracht. 4–6 Wochen nach Tumorimplantation erfolgten nach Injektion von 37 MBq [¹¹C]Cholin dynamische PET-Aufnahmen über 60 Minuten und CT-Aufnahmen. An Tag 1 und 5 nach der ersten [¹¹C]Cholin PET/CT-Untersuchung wurden acht Mäuse mit Docetaxel in einer Dosierung von 3 mg/kg Körpergewicht behandelt. Die Kontrolltiere erhielten PBS. An Tag 7, 14 und 21 nach der Therapie wurden die [¹¹C]Cholin-PET/CT-Aufnahmen wiederholt. Die Aufnahmen wurden mittels Tumor/Muskel (T/M)- Quotienten (ROI_T/ROI_M = T/M-Quotient) analysiert. Ergebnisse: Alle LNCaP-Tumoren konnten mit der [¹¹C]Cholin-PET/CT dargestellt werden. Der mittlere T/M-Quotient vor der Therapie lag für die Behandlungsgruppe bei 2,0 ± 0,2 bzw. 1,9 ± 0,2 für die Kontrollgruppe (p = 0,837). Das Wachstum der Tumoren wurde im Xenograft-Mausmodell durch Docetaxel gehemmt. Die Docetaxeltherapie führte zu einer Verringerung der [¹¹C]Cholin-Aufnahme in die Tumoren der LNCaP-Zelllinie. Der T/M_mean-Quotient der Versuchstiere war nach einer Woche 1,5 ± 0,2, nach zwei Wochen 1,3 ± 0,2 und nach drei Wochen 1,4 ± 0,2. Bei den Kontrolltieren zeigte sich keine Abnahme des T/M_mean-Quotienten. Die Änderung der [¹¹C]Cholin-Aufnahme in die Tumoren ließ sich frühzeitig ab einer Woche im Verlauf der Therapie nachweisen. Schlussfolgerung: [¹¹C]Cholin zeigt in der Kleintier-PET/CT das Potenzial als Marker zur Ermittlung des frühen Ansprechens auf eine Docetaxeltherapie in einem LNCaPProstatakarzinom-Xenograft-Mausmodell.

Keywords

Prostate cancer - xenograft model - LNCaP - small animal PET/CT - therapy response - docetaxel - choline

Schlüsselwörter

Prostatakarzinom - Xenograftmodell - LNCaP - Kleintier-PET/CT - Therapieansprechen - Docetaxel - Cholin

^* Authors contributed equally.

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