Hypoxia PET imaging techniques: data acquisition and analysis

Hypoxia is associated with poor treatment outcome in several tumor entities. Positron emission tomography (PET) offers the possibility to visualize tumor hypoxia in a spatially resolved manner using dedicated hypoxia PET tracers. The aim of this article is to review different tracers, PET acquisition methods and data analysis strategies that have been used in previous studies. A literature research has been performed in the database PubMed using the keywords “FMISO”, “FAZA”, “HX4”, “EF3/5” or “Cu-ATSM” in combination with “hypoxia”, “PET”, and “radiotherapy” in order to review the current status of hypoxia PET acquisition and data analysis strategies. A total of 141 articles were identified during the literature search. However, after exclusion of preclinical or simulation studies, 51 remained. Hypoxia PET imaging using different PET tracers was shown to have prognostic power in order to stratify patients according to outcome after chemoradiotherapy. However, most studies present small patient groups and use a variety of different PET acquisition protocols and data analysis strategies. Hypoxia PET acquisition can be performed using either static or dynamic PET acquisition. Due to the slow diffusive transport of the tracer, image acquisition needs to be performed several (2–4) h post-injection. Motivated by the low intrinsic contrast of hypoxia PET imaging, most studies use tumor-to-muscle ratios (TMR) to define areas of tumor hypoxia from static PET images, whereas dynamic scans are quantitatively analyzed using kinetic modeling. Data acquisition and analysis for hypoxia PET imaging requires standardization and harmonization, in order to empower large multicenter trials in the future, which are needed to proof the clinical benefit of personalized treatments on the basis of hypoxia PET imaging.