Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. The presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes),or as a prognostic indicator for management of the disease (e.g. stroke). Over the past two decades, a number of hypoxia radioimaging agents have been developed and tested clinically. Of these, 18F-Fmiso and 123I-IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fmiso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumour to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetics. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. 18F-Fmiso and 123I-IAZA) have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with 123I-IAZA , an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical applications.
Nitric oxide-donor/PARP-inhibitor combination: A new approach for sensitization to ionizing radiation