Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma
J. Rootman, B. Gallie, C. Kumi, N. Bussanich, B. Rogers and B. Palcic
Two new radiosensitizing drugs, SR-2508 and SR-2555, were studied for their
in vivo toxicity and absorption properties. For both drugs, 100 mg
dissolved in 0.5 mL of normal saline resulted in the maximum acceptable
level of toxicity when injected subconjunctivally in rabbit eyes as
determined by ocular and histopathologic changes. SR-2508 showed higher
ocular and systemic absorption than SR-2555. The radiosensitizing ability
of these drugs was studied using Chinese hamster ovary cells and the
retinoblastoma cell line, V79c6. Results of the in vitro radiation
experiments indicate that both drugs are comparable with misonidazole in
their radiosensitizing ability, with SR-2508 being slightly more effective
than SR-2555. Because of their relative high ocular absorption and low
toxicity in comparison with misonidazole, these two drugs, particularly
SR-2508, may be of clinical value and could be considered for adjunctive
use as radiosensitizers of hypoxic tumors such as retinoblastoma.
