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Halogenated pyrimidine sensitization of low dose rate irradiation in human malignant glioma
P W McLaughlin1, W R Mancini, P L Stetson
1Dept. of Radiation Oncology, University of Michigan Medical Center, Ann Arbor 48109.
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.