Developments in hypoxia imaging

Full text: Metabolic effects of hypoxia in tissue become apparent at O2 concentrations just below venous blood concentration (<30 mm Hg pO2), and radioresistance occurs at O2 levels below 1000 ppm (0.1%; < 0.1 mm Hg pO2). Nitroimidazoles mimic the radiosensitizing effects of O2 by forming molecular adducts under the reducing conditions present in viable hypoxic cells. This adduct formation increases hypoxic cells' radiosensitivity, and, by virtue of this hypoxia-selective accumulation, makes radiolabelled nitroimidazoles suitable for detecting and imaging hypoxic tissue. The most effective oxygen mimetics are those designed to have single electron reduction potentials (E71) of approximately -390 mV and water-lipid partition coefficients (P) between 0.1 and 10. [123I] Iodoazomycin arabinoside ([123I]IAZA) and [18F]fluoro-misonidazole ([18F]FMISO) were the first hypoxia-sensitive radiopharmaceuticals studied clinically. [18F]Fluoroetnidazole, [18F]fluoroerythronitroimidazole, [124I]iodoazomycin galactoside and [18F]FAZA are more recent sensitizers developed for PET. Of these, [18F]FAZA has shown particular promise in pre-clinical and clinical studies. In vitro and in vivo comparisons of [18F]FAZA and [18F]FMISO indicate that hypoxia-selective uptake of both is similar, but that [18F]FAZA presents higher tumor:blood concentrations and images with greater contrast, due to rapid clearance from non-target tissues both in murine models and in patients. These hypoxia-sensitive radiotracers will be discussed along with other putative hypoxia imaging agents including technetium-99m and copper-64 labelled ligands. Current clinical data will be presented. (author)