Hypoxia PET imaging beyond 18F-FMISO in patients with high-grade glioma: 18F-FAZA and other hypoxia radiotracers

Purpose High-grade gliomas are aggressive primitive brain tumors presenting aberrant vasculature, regional necrosis, and areas of hypoxia. Tumor hypoxia is associated with resistance to conventional treatment and worse prognosis. [F-18]-fluoromisonidazole (F-18-FMISO) is the most extensively investigated radiotracer for the evaluation of hypoxia. However, the use of F-18-FMISO in clinical practice has been hampered mainly due to the slow clearance of the unbound tracer from normoxic tissue and its low tumor-to-background ratio (TBR). The research community has therefore investigated other radiotracers to overcome the drawbacks of F-18-FMISO. This mini-review aims to present an update on the most relevant PET studies published in the last 15 years evaluating the utility of radiotracers for hypoxia imaging other than F-18-FMISO in high-grade glioma (HGG) patients. Methods A comprehensive computer literature search of studies was carried out in PubMed/MEDLINE database to identify the most relevant studies published in the last 15 years which investigated the utility of hypoxia PET tracers other than F-18-FMISO in the assessment of tumor hypoxia in patients with HGG. Results F-18-flouroazomycin arabinoside (F-18-FAZA) has been proposed as a valid alternative to F-18-FMISO for the assessment of hypoxia, due to its improved biodistribution and enhanced tumor-to-background ratio. Also 1-(2-[F-18]fluoro-1[hydroxymethyl]ethoxy)methyl-2-nitroimidazole(F-18-FRP170) seems a valuable hypoxia tracer in patients with brain tumor. The value of copper-diacetyl-bis(N4-methylthiosemicarbazone)(Cu-ATSM) seems controversial. Few evidences still exist regarding the utility of F-18-2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (F-18-EF5). Conclusion Hypoxia PET imaging has the potential to provide useful information for the clinicians and to guide hypoxia tailored treatments. According to the present literature, the most promising hypoxic tracer seems to be F-18-FAZA, but well-designed and wide trials to validate hypoxia radiotracers and evaluate their clinical utility in daily practice are still lacking.