Radiosensitization of hypoxic cells in vitro and in vivo by AK-2123

The effects of AK-2123 (a 3-nitro-1,2,4-triazole bearing CH2CONHC2H4OCH3 at the N1-position) to sensitize hypoxic cells in vitro and in vivo were investigated using the FSaII tumor of C3Hf/SED mice. The Do value of survival curves of the in vitro grown cells was 1.03±0.05 Gy under oxic conditions. The Do of the hypoxic cells was 2.54±0.15 Gy and it decreased to 1.34±0.06 Gy in the presence of 1 mM of AK-2123 for 1 hr prior to irradiation. When the tumors grown sc in the legs of mice were irradiated, dispersed to single cells and cultured in vitro, the Do value of survival curves of the tumor cells from air breathing mice was 2.93±0.63 Gy. An ip injection of AK-2123 at 270 mg/kg (10% of LD50 dose) 20 min before the X-irradiation resulted in the survival curve with a Do of 2.38±0.33 Gy. The ER with 270 mg/kg of AK-2123 for the reduction of cell survival to 0.1% was about 1.4. An ip injection of AK-2123 at 270 mg/kg 20-30 min prior to exposure of the tumors to X-rays significantly enhanced the growth delay of tumors induced by X-irradiation with 20 or 30 Gy, but not that with 10 Gy. Similar growth delay was observed in SCK tumors grown sc in the legs of A/J mice. (author)