Figure 9. [18F]-MISO

The majority of hypoxia PET tracers belong to a group of compounds termed nitroimidazoles.

18F-Fluoromisonidazole (18F-FMISO) was the first nitroimidazole-based radiotracer to be developed for hypoxia PET imaging.

Nitroimidazoles enter cells by diffusion and are reduced inversely correlated with oxygen tension. In the presence of oxygen they are able to leave the cell again, but under hypoxic conditions nitroimidazoles become reduced and will be irreversibly trapped within the cells.

18F-FMISO enters the cell by passive diffusion, where it is reduced by nitroreductase enzymes to become trapped in cells with reduced tissue oxygen partial pressure. When oxygen is abundant in normally oxygenated cells, the parent compound is quickly regenerated by reoxidation and metabolites do not accumulate. However, in hypoxic cells, the low oxygen partial pressure prevents reoxidation of 18F-FMISO metabolites, resulting in tracer accumulation. Because FMISO only accumulates in hypoxic cells with functional nitroreductase enzymes, FMISO will only accumulate in viable cells but not dead necrotic cells.

Quantification of 18F-FMISO ratioactivity in normal tissue achieves equality with plasma levels within 30 minutes, but selective retention of 18F-FMISO is observed in hypoxic tissue by 1 hour after injection and persists until 2.5 hours,  resulting in favorable information about the hypoxic volume being assessed.


- Lee ST, et al. Hypoxia Positron Emission Tomography Imaging With 18F-Fluoromisonidazole. Semin Nucl Med; 2007; 37:451-461.
- Li F, Joergensen J, et al. Kinetic modeling in PET imaging of hypoxia; Am J Nucl Med Mol Imaging 2014;4(6):490-506