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.

Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non–Small Cell Lung Cancer

“…The most widely used surrogate metric of tumor hypoxia in 18 F-FMISO PET is its TBR derived from a single late-time-point image. Investigators have reported times from 2-4 h after 18 F-FMISO administration (12,27,28). An image voxel is considered to be hypoxic if TBR exceeds a predetermined value, usually 1.2-1.4 (18,27).…”

“…Investigators have reported times from 2-4 h after 18 F-FMISO administration (12,27,28). An image voxel is considered to be hypoxic if TBR exceeds a predetermined value, usually 1.2-1.4 (18,27). This approach, although simple to implement, may misidentify hypoxic voxels, a consequence of the slow 18 F-FMISO clearance from regions of high tumor perfusion.…”

Radiotherapy response evaluation using FDG PET-CT—established and emerging applications

“…Alternative tracers which act as surrogates for hypoxia include fluorine-18 fluoroazomycin-arabinofuranoside and copper-64 diacetyl-bis(N4-methylthiosemicarbazone). Both tracers have more favourable pharmacokinetics than fluoromisonidazole and hold promise for further research (an overview can be seen in the study of Feling et al 2015 79 ). Cellular mechanisms involved in tumour response to treatment include a reduction in cell proliferation, which can be assessed using fluorothymidine PET-CT and an increase in apoptosis, which could be evaluated using a specialized tracer such as fluorine-18 2-(5-fluoro-pentyl)-2-methyl-malonic acid, as a surrogate biomarker.…”

Assessing Oxygenation Response to Eribulin in a Patient with Recurrent Breast Cancer after Resistance to Endocrine Therapy

“…However, the longterm effectiveness of endocrine therapy is limited by the development of endocrine resistance, which is strongly associated with hypoxia in the tumor microenvironment [6]. A noninvasive technology for quantifying tumor hypoxia is 18 F-fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) imaging [7]. Investigators have reported FMISO uptake as a robust measure of intracellular hypoxia, and reduced hypoxic activity after endocrine therapy has been identified as a good predictive marker of clinical response in patients with HR-positive metastatic breast cancer [8].…”