Scintigraphic imaging with 123 IAZA: a predictive in vivo test for tissue hypoxia

Full text. Hypoxia defines a metabolic state in which tissue concentrations of O2 lie between normal physiological levels (normoxia) and complete lack of oxygen (anoxia). Regional hypoxia can lead to, or be associated with a number of clinically important pathologies. Adequate assessment of hypoxia is important for selection of appropriate therapy and for prognostic evaluation of the condition. Predictive tests for hypoxia can be based on the direct measurement of O2 with the oxygen electrode, but there are substantial barriers to accurate in vivo measurement of O2, including limited access to some tissues and/or the constant movement of others. Hypoxia can be diagnosed, and perhaps quantified, by measuring the reductive binding of compounds that have high electron affinities. The uptake of electron-affinit oxygen-mimetics such as 1-(5-iodoarabinofuranosyl) - 2-nitroimidazole (IAZA) has been shown to reflect tissue hypoxia in vivo. 123 IAZA has been used clinically to detect and delineate tissue hypoxia in a number of conditions. This paper reviews the fundamental mechanisms that lead to the selective binding nitroimidazoles by hypoxic tissues. The biological properties of these compounds will be demonstrated using in vitro and pre-clinical in vivo data. Clinical data for 123 IAZA will be reported, emphasizing pharmacokinetics and radiation dosimetry, together with a review of clinical imaging with 123 IAZA in oncology, diabetes and brain trauma