Introduction 1 2 Overview of tumour hypoxia & its importance 3 4 2 2 5 6 8 2 9 10 11 1 12 Fig. 1 4  2 2 13 2 14 2 15 2 1 16 Clinical imaging of hypoxia As tumour hypoxia is an important biological characteristic and there is no good or easy clinical way to predict its presence, it has been suggested that imaging may be a good way of non-invasively selecting cancer patients who would benefit from treatments that overcome, circumvent or take advantage of the presence of hypoxia. Since tumour hypoxia is a key mechanism that leads to radioresistance, it has been repeatedly suggested that a hypoxia mapping technique could be integrated with conformal radiotherapy techniques to improve target delineation and dose delivery; this is discussed in more detail below. Imaging could also be used to document whether or not and the extent to which reoxygenation of tumours occurs during radiotherapy. Key requirements of any method that evaluates tumour hypoxia include non-invasive assessments that allow serial changes during treatment to be monitored and evaluation of heterogeneity between and within tumours. 17 18 2 2 2 2 18 60/64 1 Table 1 Comparison of techniques for evaluating human tumour hypoxia Technique and key references Invasive investigation Requires injection Measures Clinically Validated in RT General availability (1–5; poor-wide) Monitors changes in pO2 18 F-MISO PET 19 24 51 53 No Yes Hypoxia ± 3 No 18 F-AZA PET  54 No Yes Hypoxia No 2 No 18 F-EF5 PET 55 No Yes Hypoxia ± 2 No 64Cu ATSM 25 26 28 34 35 No Yes Hypoxia ± 3 No BOLD-MRI 36 No No [dHb] in RBCs Yes 4 Yes Polorographic electrode 6 8 Yes No pO2 Yes 2 Yes 18 18 18 19 18 2 18 2 2 3 Fig. 2 18 18 18  Fig. 3 18 18 18 18 2 2 18 2 45  18 18 2 18 18 3 18 18 14 18 20 21 22 24 18 Cu-ATSM 4 25 32 4 60 4 60 64 1/2 33 64 Fig. 4 a b 60 60  34 35 60 60 34 35 BOLD-MRI 2 2 36 2 2 2 5 Fig. 5 2 2 2 2 2 2 2  37 2 2 2 2 2 2 2 38 39 2 2 2 2 2 2 40 41 37 2 2 2 2 42 43 2 2 40 41 Hypoxia guided radiotherapy 44 45 46 60/64 47 15 6 18 20 Fig. 6 15  18 48 49 18 7 Fig. 7 2  Challenges for hypoxia imaging techniques 50 Quantification reproducibility heterogeneity 18 18 Conclusions To summarise, tumour hypoxia is common and its effects represents a significant challenge to the curability of human tumours, leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationship between these techniques needs to be better defined; human validation of the utility of hypoxia imaging is sparse at best. Anti-hypoxia therapies exist in the clinic and more are on their way. Either they don’t work very well or we don’t know how to use them optimally. Hypoxia imaging may allow better definition of a sub-population of cancer patients that would benefit for novel anti-hypoxia directed therapies.