Artikel
Systemic treatment with [211At] astatine-phenylalanine enhances survival of rats with intracranial glioblastoma
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Increased amino acid transport in brain tumors is used for diagnostic purposes. It has been shown that the alpha emitter astatine-211 labelled to phenylalanine (At-Phe) is taken up by glioblastoma cells in vitro. Here, we tested whether systemic intravenous treatment with At-Phe would have a beneficial effect in rats after intracranial implantation of a glioblastoma cell line.
Methods: At-Phe was prepared via nucleophilic halogen exchange on L-iodophenylalanine. The rat glioblastoma cell line BT4Ca was implanted into the prefrontal cortex of female BDIX rats by stereotaxic microinjection (10.000 cells/3 µl; n=83). At-Phe (2 MBq) or phosphate buffered saline (PBS) were injected intravenously three days after implantation. A third group was treated twice, on days 3 and 10 after implantation. The rats' health condition was assessed each day by using a scoring system (e.g. weight and motor reflexes) and rats were sacrificed when they showed a prefinal status. Additionally, rats were sacrificed on days 6, 10, 13 and 17 after transplantation to measure the tumor volume and area of necrosis. Furthermore, the proliferation index was assessed after immunohistological staining for Ki-67.
Results: The mean survival time of the rats that received two applications of At-Phe was significantly higher compared to the control group (p<0.05). The score analysis showed that At-Phe-treated rats had significantly better health condition compared to PBS-treated rats (p<0.05). Analysis of the tumor volume on days 6, 10, 13 and 17 after transplantation showed no differences between the groups, but rats with a prefinal status had a significantly larger tumor than rats in good health condition (p<0.05). Overall, the proliferation index was not different between groups, but necrosis was marginally larger after At-Phe treatment (p<0.05 on day 10).
Conclusions: Intravenous treatment with At-Phe enhanced the survival time of rats with intracranial glioblastomas and improved health condition in comparison to controls. These results encourage studies on using a local treatment of intracranial glioblastoma with At-Phe, either by repeated local injection or by intracavital application after tumor resection.