Review Article

Hypoxia in Head and Neck Cancer in Theory and Practice: A PET-Based Imaging Approach

Table 1

Techniques for tumour hypoxia evaluation/measurement.

TechniqueCharacteristics

Polarographic electrode (Eppendorf oxygen electrode)Direct and invasive technique involving a fine-needle electrode (cathode) for tumour hypoxia measurement. The current between the cathode and the reference electrode is directly proportional to tissue pO2.

Cryospectrophotometry Indirect, histomorphometric assay of oxygen levels in tumour vasculature assessed on frozen tissue samples.

Microvessel density (angiogenesis assessment)Indirect way to assess hypoxia using immunohistochemical techniques for counting blood vessels that were previously labeled with endothelium-specific markers.

DNA strand break assay (comet assay)Indirect way to assess tumour hypoxia through DNA strand breaks after radiation exposure and fluorescent staining, based on the fact that oxic cells get more damage than hypoxic cells. The DNA fragments detached from the nucleus resemble the tail of a comet.

Endogenous hypoxia markersIndirect method to evaluate the hypoxic fraction in tumours. Hypoxia inducible factor (HIF)-1 alpha, glucose transporter 1 (GLUT 1), and carbonic anhydrase 9 (CA 9) have been identified as proteins, which under hypoxic exposure induce the transcription of several genes.

Exogenous hypoxia markersIndirect method to evaluate tumour hypoxia (using biopsies). Exogenous markers are nitroaromatic compounds (pimo-, miso-, eta-nidazole) which selectively bind to hypoxic cells.

Oximetry with electron paramagnetic resonanceNoninvasive and direct method to quantify pO2 in tissue using stable nitroxides that interact with molecular oxygen.

Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI)Noninvasive method for evaluation of hypoxia through correlation of BOLD signals with pO2.

Positron emission tomographyNoninvasive and direct method to evaluate hypoxia via injection of hypoxia-specific radiotracers.