In Vitro


The molecule under development, ACD-101 is a small amino acid derivative which is taken up by malignant gliomas with high avidity. It has been shown to be retained by human glioma cells in vitro and in vivo for prolonged periods. ACD-101 possesses a dose-dependent anti-cancer action in human glioma cell lines in vitro which is cytostatic in type. ACD-101 contains an iodine atom, allowing for radioactive labelling for diagnostic and therapeutic puposes (123 Iodine, 124 Iodine, or 131 Iodine, respectively).

In addition to the cytostatic effect ACD-101 has an intrinsic radiosensitizer effect which can synergistically increase tumor killing in connection with both standard external field radiation therapy (XRT), or intracellular endo-radiation therapy (ERT), using 131I- ACD-101.

In human glioma cell lines treated with XRT in vitro, unlabelled ACD-101  increases cell death via both pathways, primary necrosis and apoptosis (secondary, programmed cell death) in a dose-dependent fashion.

Efficient cellular killing in human glioblastoma cells in vitro

Incubation with 1.0 µCi/ml 131I-ACD-101 for 24 h

Key result:
  • More than 85 % cells die within 24 h

Effects of external field radiation alone vs. in combination with endoradio-therapy on survival and growth of human glioblastoma cells in vitro


Effect on external irradiation alone on cell growth

XRT alone (0 – 15 Gy), maximum human dose : 60 Gy


Effect on external irradiation plus endoradiotherapy on cell growth
ERT with 1.0 µCi/ml131I-ACD-101 + XRT (0 – 15 Gy)

Key results:
  • XRT (maximum human dose 60 Gy) has a cytostatic (growth inhibiting) effect only
  • ERT with 1.0 µCi/ml 131I-ACD-101 has a cytocidal (cell killing) effect, which is further enhanced by simultaneous XRT

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01326 Dresden
Germany

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