Misonidazole

Misonidazole is a nitroimidazole compound that was investigated as a radiosensitizer in cancer radiotherapy. It was developed to enhance the effect of ionizing radiation on hypoxic tumor cells, which are more resistant to radiation than well-oxygenated cells.

Mechanism of action is based on bioreductive activation. In hypoxic cells, misonidazole undergoes enzymatic reduction of its nitro group, forming reactive intermediates that exacerbate radiation-induced DNA damage. The presence of oxygen competes with this reduction, reducing the radiosensitizing effect in normoxic tissue. As a result, misonidazole was studied for its potential to selectively sensitize hypoxic tumor regions.

Clinical use and status: Misonidazole was evaluated in combination with external beam radiotherapy for various cancers, but its development was limited by dose-limiting neurotoxicity, including peripheral neuropathy, crawling sensations, difficulty in walking, dizziness, and in some cases more severe neurologic effects. Because of modest therapeutic gains relative to the toxicity risk, misonidazole never achieved routine clinical adoption and is no longer widely used as a cancer radiosensitizer.

Imaging and research applications: Related derivatives and labeled forms of misonidazole have been used in research and imaging to map tumor hypoxia, aiding studies of tumor biology and treatment planning in some settings.

Pharmacokinetics and safety: In trials, administration was by oral or intravenous routes; misonidazole is distributed systemically and eliminated with hepatic metabolism and renal excretion. Safety concerns led to restricted clinical use, and it is now primarily of historical and research interest in the field of tumor hypoxia.