Bromomisonidazole: Synthesis and characterization of a new radiosensitizer

J. S. Rasey, Kenneth Krohn, S. Freauff

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 137Cs γ rays; sensitizer enhancement ratios of 1.9 (D0 (- sensitizer)/[D0 (+ sensitizer)] were obtained for both drugs. Toxicity studies (LD50/2(days)) showed that 4-bromomisonidazole is more toxic (LD50 50 = 9.05 mmole/kg = 1.82 mg/g) in C3H/HeJ mice. Biodistribution studies of 4-[82Br]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-[82Br]bromomisonidazole and [82Br]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 may 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.

Original languageEnglish (US)
Pages (from-to)542-554
Number of pages13
JournalRadiation Research
Volume91
Issue number3
StatePublished - 1982
Externally publishedYes

Fingerprint

Misonidazole
tumors
neoplasms
synthesis
mice
Lethal Dose 50
Neoplasms
lethal dose 50
toxicity
blood
partitions
drugs
bromination
octanol-water partition coefficients
Octanols
partition coefficients
imidazoles
Inbred C3H Mouse
Poisons
Halogenation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Bromomisonidazole : Synthesis and characterization of a new radiosensitizer. / Rasey, J. S.; Krohn, Kenneth; Freauff, S.

In: Radiation Research, Vol. 91, No. 3, 1982, p. 542-554.

Research output: Contribution to journalArticle

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