The synthesis and radiolabelling of novel markers of tissue hypoxia of the iodinated azomycin nucleoside class.

Knowledge about the oxygenation of human tumors and its importance in the response to radiotherapy is crucial to the effort to develop improved treatment methods for radiotherapy. The measurement of oxygenation of human tumors and correlations with response to radiotherapy were the subjects of a recent workshop sponsored by the National Cancer Institute. The following methods for measuring oxygen or hypoxia, or a parameter related to either, were presented: polarographic oxygen electrodes, the comet and alkaline elution assays for radiation-induced DNA damage, nitroimidazole binding assays, hemoglobin saturation assays, magnetic resonance spectroscopy, electron spin resonance spectroscopy, phosphorescence imaging, and an assay for tumor interstitial pressure. The electron spin resonance, alkaline elution, and phosphorescence imaging methods have not been used in human tumors. The comet assay, nitroimidazole binding assays, magnetic resonance spectroscopy, cryospectroscopy, and near-infrared spectroscopy have been employed in human tumors, but correlations to treatment response have not been made. Polarographic measurements have indicated that the presence of hypoxia correlates with a poor response to radiotherapy in cervical cancers, but additional data are needed on early-stage disease, and with long-term follow-up on local control and survival. If these confirm the correlation between hypoxia and poor response to radiotherapy, additional tumor sites should be studied. Future clinical trials of treatments that sensitize, exploit, or kill hypoxic cells should identify and include the individual patients with hypoxic tumors. Fundamental unanswered questions regarding the assessment of tumor oxygenation concern the need for invasive procedures, the spatial resolution needed for prediction of response to radiotherapy, the importance of reoxygenation, differences between tumors in rates and degrees of reoxygenation, whether measurements made during a course of therapy are of value, and correlations among methods and with other predictive assays such as intrinsic radiosensitivity and potential doubling time.