FDG - A marker of tumour hypoxia? A comparison with [18F] fluoromisonidazole and pO2-polarography in metastatic head and neck cancer
ABSTRACT Experimental data suggest that the accumulation of [(18)F]fluorodeoxyglucose (FDG) in malignant tumours is related to regional hypoxia. The aim of this study was to evaluate the clinical potential of FDG positron emission tomography (PET) to assess tumour hypoxia in comparison with [(18)F]fluoromisonidazole (FMISO) PET and pO(2)-polarography.
Twenty-four patients with head and neck malignancies underwent FDG PET, FMISO PET, and pO(2)-polarography within 1 week. Parameters of pO(2)-polarography were the relative frequency of pO(2) readings <or=2.5 mmHg, <or=5 mmHg and <or=10 mmHg, respectively, as well as the mean and median pO(2).
We observed a moderate correlation of the maximum standardised uptake value (SUV) of FDG with the tumour to blood ratio of FMISO at 2 h (R=0.53, p<0.05). However, SUV of FDG was similar in hypoxic and normoxic tumours as defined by pO(2)-polarography (6.9+/-3.2 vs 6.2+/-3.0, NS), and the FDG uptake was not correlated with the results of pO(2)-polarography. The retention of FMISO was significantly higher in hypoxic tumours than in normoxic tumours (tumour to muscle ratio at 2 h: 1.8+/-0.4 vs 1.4+/-0.1, p<0.05), and the FMISO tumour to muscle ratio showed a strong correlation with the frequency of pO(2) readings <or=5 mmHg (R=0.80, p<0.001).
These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.
- SourceAvailable from: Jeho Jeong
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- "The oncolytic appetite for glycolysis is thought to be caused by a number of genetic or possibly epigenetic changes that drive malignancy  . Many studies have been carried out to correlate FDG uptake with various physiological parameters, such as hypoxia, proliferation, blood flow, histology, and differentiation , utilizing FDG-PET and immunohistochemical methods      . However, although several studies have shown the relationship between the FDG uptake and hypoxia or proliferation , the underlying mechanism of FDG uptake in a tumor is still unclear. "
ABSTRACT: High fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tumors has often been correlated with increasing local failure and shorter overall survival, but the radiobiological mechanisms of this uptake are unclear. We explore the relationship between FDG-PET uptake and tumor radioresistance using a mechanistic model that considers cellular status as a function of microenvironmental conditions, including proliferating cells with access to oxygen and glucose, metabolically active cells with access to glucose but not oxygen, and severely hypoxic cells that are starving. However, it is unclear what the precise uptake levels of glucose should be for cells that receive oxygen and glucose versus cells that only receive glucose. Different potential FDG uptake profiles, as a function of the microenvironment, were simulated. Predicted tumor doses for 50% control (TD50) in 2 Gy fractions were estimated for each assumed uptake profile and for various possible cell mixtures. The results support the hypothesis of an increased avidity of FDG for cells in the intermediate stress state (those receiving glucose but not oxygen) compared to well-oxygenated (and proliferating) cells.Computational and Mathematical Methods in Medicine 09/2014; 2014:847162. DOI:10.1155/2014/847162 · 1.02 Impact Factor
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- "Additionally, 18 F-FDG has also been proposed as a surrogate marker of tumor hypoxia following the potential increased cell metabolism from oxidative phosphorylation to glycolysis when oxygen level drops . This induce an increase in the uptake of glucose but despite this well-characterized connection, preclinical and clinical studies have reported conflicting results; but in general 18 F-FDG cannot be considered as a consistent surrogate marker of hypoxia in tumors      . "
ABSTRACT: Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia.American Journal of Nuclear Medicine and Molecular Imaging 01/2014; 4(6):490-506. · 3.25 Impact Factor
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ABSTRACT: Patients with squamous cell carcinomas (SCCs) of the head and neck are increasingly treated nonsurgically. Imaging plays a critical role in helping define the targets for radiation therapy, especially intensity-modulated radiation therapy, in which the dose gradients are steep. Anatomic imaging with conventional modalities, particularly computed tomography (CT), has been used in patients with head and neck SCCs, but this approach has limitations. Functional imaging techniques, including positron emission tomography (PET) combined with CT or magnetic resonance (MR) imaging, offer complementary information and can be used noninvasively to assess a range of biomarkers in patients with head and neck SCCs, including hypoxia, cell proliferation and apoptosis, and epidermal growth factor receptor status. These biologic markers can be monitored before, during, and after treatment to improve patient selection for specific therapeutic strategies, guide adaptation of therapy, and potentially facilitate more accurate assessment of disease response. This article discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning and reviews the potential of molecular imaging biomarkers for response assessment and therapy adaptation. The uses of PET tracers for imaging cellular processes such as metabolism, proliferation, hypoxia, and cell membrane synthesis are explored, and applications for MR techniques such as dynamic contrast material-enhanced imaging, diffusion-weighted imaging, blood oxygenation level-dependent imaging, and MR spectroscopy are reviewed. The potential of integrated PET/CT perfusion imaging and hybrid PET/MR imaging also is highlighted. These developments may allow more individualized treatment planning in patients with head and neck SCCs in the emerging era of personalized medicine. © RSNA, 2013.Radiographics 11/2013; 33(7):1909-29. DOI:10.1148/rg.337125163 · 2.73 Impact Factor