Table 2.

Trials involving hypoxia-specific PET imaging in head and neck cancer over the last 10 years.

Radiotracer	Reference	Trial and aim	Results
18F-MISO	Rischin et al. 2006 [16]	TROG randomized trial (45 patients)  To determine the association between tumour hypoxia, treatment regimen, and locoregional failure in advanced HNC	18F-MISO-detected hypoxia is associated with high locoregional failure in patients not receiving tirapazamine.
	Kikuchi et al. 2011 [17]	Clinical study (17 patients)  To evaluate the role of 18F-MISO as a predictor of treatment outcome in HNC	Local control after radiotherapy was significantly lower in patients with high uptake than in those with low tracer uptake. Pretreatment scan with 18F-MISO may predict treatment outcome.
18F-FAZA	Souvatzoglou et al. 2007 [18]	Phase I trial (11 patients)  Feasibility of 18F-FAZA for hypoxia imaging in HNC patients	Feasible for clinical use and offers adequate image quality for hypoxia assessment.
	Postema et al. 2009 [19]	Phase I trial (9 HNC patients out of 50 overall cancer patients)  To demonstrate the safety and biodistribution pattern of 18F-FAZA in patients with HNC, lung cancer, gliomas, and lymphomas	Clear uptake of 18F-FAZA was observed in 6 out of 9 HNC patients; good imaging properties; good tumour-to-blood ratio. Promising agent for hypoxia imaging in HNC.
18F-EF3	Mahy et al. 2008 [20]	Phase I trial (10 patients)  To assess the pharmacokinetics, biodistribution, and metabolism (324 MBq versus 1,134 MBq)	Uptake and retention in tumour was observed; no difference between the radioactivity groups; no side effects; safe and feasible.
18F-EF5	Komar et al. 2008 [21]	Phase I trial (15 patients)  To determine the optimal PET protocol for 18F-EF5 as a hypoxia imaging agent	Initial 18F-EF5 uptake is governed by blood flow; later phase uptake is hypoxia specific (optimal detection time is 3 h after injection); warranting more study.
18F-HX4	Chen et al. 2012 [22]	Phase I trial (12 patients)  To evaluate the feasibility of HX4 compared with 18F-MISO	HX4 possibly has higher sensitivity and specificity and shorter injection-acquisition time (1.5 h) than 18F-MISO
Cu-ATSM	Minagawa et al. 2011 [23]	Phase I/II trial (17 patients)  To evaluate the relationship between 62Cu-ATSM tumour uptake and chemoradiotherapy	62Cu-ATSM SUVmax greatly differed between patients with and without residual disease. 62Cu-ATSM could be a predictor of tumour response to treatment.
	Grassi et al. 2014 [24]	Preliminary prospective study (11 patients)  To assess the efficacy of pretreatment 64Cu-ATSM as a prognostic factor and its role as a marker of disease progression	64Cu-ATSM showed high sensitivity but low specificity in predicting response to chemoradiotherapy. There were no differences between early and late scans.

HNC: head and neck cancer.