A new potent hypoxic cell sensitizer, a
2-nitroimidazole nucleoside analogue having methoxyglycerol as a
sugar moiety at the N-1 position of the
imidazole ring (RP-170), has been synthesized. Its radiosensitizing activities in vitro and in vivo were investigated and compared with those of
misonidazole (MISO) and
etanidazole (SR-2508). As might be expected from the almost identical electron affinities of the three compounds, they were equally effective against hypoxic EMT6 cells in vitro. The in vivo-in vitro excision analysis showed that
RP-170 was also as effective as MISO and
etanidazole to radiosensitize solid
tumor cells in vivo. An intraperitoneal administration of 200 mg/kg of
RP-170 and an
intravenous administration of the same dose of
etanidazole showed an equal sensitizer-enhancement ratio of 1.51 to solid EMT6/KU
tumors. Its effectiveness was also demonstrated by growth delay assay using solid SCCVII
tumors. As predicted from the low partition coefficient,
RP-170 and
etanidazole showed apparently lower toxicity in vivo than MISO; their LD50/14 were 4.3, 4.8, and 1.8 g/kg in our experiment, respectively. Moreover,
RP-170 showed fast clearance from serum in mice (t1/2 = 10.24 min) and poor penetration into neural tissues. Although
RP-170 does not show any advantages over
etanidazole in terms of sensitization or toxicity,
RP-170 might be preferable under certain circumstances because it can be given orally.