Halogenated pyrimidine sensitization of low dose rate irradiation in human malignant glioma.
PURPOSE: To determine the potential advantage of combining halogenated pyrimidine radiosensitization and continuous low dose rate irradiation in human malignant glioma. METHODS AND MATERIALS: An established glioma line (U-251) was incubated with 5-bromo-2-doxyuridine (BrdUrd) at clinically achievable concentrations at three dose rates of interest--100 cGy/min (typical of external beam therapy), 43 cGy/hr (typical of temporary afterloaded implants), and 12 cGy/hr (typical of permanent implants). RESULTS: After exposure to 1 microM BrdUrd, the greatest enhancement ratio was seen at the 12 cGy/hr dose rate, implying a BrdUrd induced inverse dose rate effect independent of a G2M block. Under these conditions, the mean inactivation dose after 1 microM BrdUrd exposure was equivalent for 100 cGy/min and 12 cGy/hr. CONCLUSION: These results support the use of halopyrimidines as sensitizers of temporary afterloaded and permanent implants.
McLaughlin, PW; Mancini, WR; Stetson, PL; Greenberg, HS; Nguyen, N; Seabury, H; Heidorn, DB; Lawrence, TS
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