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• W2077778119 abstract "Abstract Recently a new class of drugs has been identified by Adams et al. at the Gray Laboratory, which act as specific radiosensitizers of hypoxic cells. This sensitization results from their high electron affinity, and their presence at the time of irradiation abolishes the protection afforded by hypoxia. Amongst the various nitro-heterocyclic compounds that have been tested the nitroimidazoles seem to give the greatest sensitization in vivo . The 5-nitroimidazole nnetronidazole, and its 2-nitro derivative Ro-07-0582 have both been shown to be potent radiosensitizers, and to have a low toxicity in vivo . Tumor studies with Ro-07-0582 have been performed on at least 12 different experimental animal tumors, using a variety of endpoints, e.g. tumor regrowth delay, local control, and cell survival assays in vitro or in vivo after in vivo irradiation. The degree of sensitization achieved depends upon the drug dose administered, over the range 0.1–1.5 mg/g body weight. All tumors that contain hypoxic cells have been sensitized to single doses of radiation, often showing an enhancement ratio of 2.0. Normal tissues that are well oxygenated are not sensitized. Studies with fractionated doses of drug and radiation have also been performed on five tumor lines. Of these, three tumors have continued to show a considerable therapeutic advantage for treatments with the drug. The use of Ro-07-0582 with X-rays has been compared with the fast neutron beam from the MRC Cyclotron at Hammersmith Hospital on two mouse tumor lines. The X-ray plus sensitizer treatments were as effective as the fast neutron treatments. Fast neutrons used together with Ro-07-0582 were more effective than any of the other treatments. The time of administration of the drug relative to irradiation is critical. It must be present at its maximum concentration at the time of irradiation. This occurs between 15 and 60 min in mice, where the biological half-life is short (1–1.5 hr). In man there is a plateau in serum concentration between 1 and 5 hr after administration. Because of this and the longer half-life (10–18 hr), the timing is less critical. In addition to the direct radiosensitization there is a specific cytotoxicity for hypoxic cells ff the exposure to the drug is long enough. This effect is small compared to the radiosensftization, but it will be of more importance in man than in the mouse, because of the difference in half-lives of drug in the serum. This cytotoxicity can be greatly enhanced by moderate hyperthermia. It would represent systemic chemotherapy for hypoxic (probably non-proliferating) cells throughout the body." @default.
• W2077778119 created "2016-06-24" @default.
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• W2077778119 date "1978-01-01" @default.
• W2077778119 modified "2023-09-26" @default.
• W2077778119 title "Radiosensitization of solid tumors by nitroimidazoles" @default.
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• W2077778119 doi "https://doi.org/10.1016/0360-3016(78)90130-x" @default.
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