Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma

Arch Ophthalmol. 1986 Nov;104(11):1693-7. doi: 10.1001/archopht.1986.01050230131048.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Animals
  • Cell Line
  • Etanidazole
  • Eye / drug effects
  • Eye / metabolism*
  • Eye Neoplasms / drug therapy*
  • Eye Neoplasms / metabolism
  • Female
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Nitroimidazoles / adverse effects
  • Nitroimidazoles / metabolism
  • Nitroimidazoles / therapeutic use
  • Rabbits
  • Radiation-Sensitizing Agents / metabolism
  • Radiation-Sensitizing Agents / therapeutic use*
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / metabolism

Substances

  • Nitroimidazoles
  • Radiation-Sensitizing Agents
  • Etanidazole
  • SR 2555