Imaging tumour hypoxia with positron emission tomography

Abstract

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.

Figure 1

Structures and logP-values of PET hypoxia radiotracers. The logP-value (partition coefficient) of each radiotracer is shown in the parentheses. Positive logP-values indicate a lipophilic molecule, whereas negative logP-values represent a hydrophilic molecule.

Figure 2

Tumour-to-reference tissue ratios and range in different tumour sites for the PET hypoxia tracers discussed in this review. For nitroimidazole-based analogues (FMISO, FAZA, FETNIM, HX4, FRP-170) values are given for acquisitions performed at 120 min post tracer administration. For Cu-ATSM, values are presented for scans conducted 60 min.

Figure 3

(A) Transverse ¹⁸F-FMISO fused PET/CT overlay image acquired at baseline of a patient with metastatic renal cell carcinoma (mRCC) in the neck acquired at 2.5–3 h p.i (image courtesy of Professors Tim Eisen and Duncan Jodrell, University of Cambridge, UK). (B) ⁶⁴Cu-ATSM fused PET/CT overlay image of a patient with advanced laryngeal squamous cell carcinoma (LSCC) at 80–90 min p.i. The transverse slice includes primary tumour and local lymph node (image courtesy of Dr Anastasia Chalkidou, King's College London, UK).