Tumour hypoxia: lessons learnt from preclinical imaging

Purpose: In tumour, the imbalance between oxygen supply and demand leads to hypoxia, which represents a negative prognostic factor associated with aggressive tumour phenotype and therapy resistance. This review provides an overview of the use of positron emitter-labelled radiopharmaceutical used to image hypoxia in preclinical models of cancer. Methods: A critical and comprehensive PubMed search was performed identifying articles related to PET imaging for hypoxia assessment in preclinical setting from January 2007 up to January 2017. Results: We have considered and described a total of 54 original articles, exploring tumour-associated hypoxia in preclinical models. Results underlined the potential application together with the advantages and pitfalls of the use of PET in preclinical research. Multi-target imaging allowed to better define the relationship between hypoxia and other biological hallmarks of tumour; imaging of hypoxia was proved as a useful tool for lesions stratification and response prediction to radiotherapy; however, cutoff indexes were identified in few studies. Hypoxia PET showed remarkable tracer delivery limitations in the study of vascular disrupting agents but suggested the potential use of PET as a marker of response or resistance to anti-angiogenics. Finally, the effect of anaesthesia on tracer kinetics and tumour oxygenation as well as perfusion dependency in tracer uptake should be carefully evaluated to avoid artefactual results. Conclusions: Preclinical studies highlight the advantages and the limitations of the available hypoxia-radiotracers and their potential usefulness for the evaluation of treatments outcome and radiotherapy planning.