Bromomisonidazole: synthesis and characterization of a new radiosensitizer.
Bromomisonidazole: synthesis and characterization of a new radiosensitizer.
复制标题
溴米异硝唑：新型放射增敏剂的合成和表征。
DOI：
10.2307/3575891
复制
发表时间：
1982
影响因子：
3.4
通讯作者：
S. Freauff
中科院分区：
文献类型：
--
作者：
J. Rasey;K. Krohn;S. Freauff
4-Bromomisonidazole has been synthesized by direct bromination of misonidazole and has been characterized chemically and in animals. The compound is highly stable in vitro and in vivo and, relative to misonidazole, has an increased partition coefficient of 2.9 in octanol-water. In EMT-6/UW tumor-bearing mice, misonidazole and 4-bromomisonidazole (1 mmole/kg) sensitize tumors equally well to /sup 137/Cs ..gamma.. rays; sensitizer enhancement ratios of 1.9 (D/sub 0/ (- sensitizer)/D/sub 0/ (+ sensitizer)) were obtained for both drugs. Toxicity studies (LD/sub 50///sub 2 days/) showed that 4-bromomisonidazole is more toxic (LD/sub 50/<6.5 mmole/kg) than misonidazole (LD/sub 50/=9.05 mmole/kg=1.82 mg/g) in C3H/HeJ mice. Biodistribution studies of 4-(/sup 82/Br)bromomisonidazole in mice reveal that iv and ip routes of administration are equally effective in delivering the drug to tissue. The tumor:blood ratio reaches a maximum at 40 min postinjection. Tumor:blood ratios are similar to those for misonidazole; tumor:brain ratios are generally higher. Biodistributions of 4-(/sup 82/Br)bromomisonidazole and (/sup 82/Br)bromide ion are significantly different, suggesting that the label remains on the imidazole ring. Bromomisonidazole is stable, appears to retain its label in vivo, and has biodistribution and toxicity characteristics consistent with its high partition coefficient. It is at least as good a sensitizer as misonidazole. It maymore » retain other properties of misonidazole, which may make it directly cytotoxic to hypoxic cells or capable of binding in such cells. These properties suggest that it may be useful for imaging hypoxic cells in tumors as well as other tissues.« less
