FDG - A marker of tumour hypoxia? A comparison with [18F] fluoromisonidazole and pO2-polarography in metastatic head and neck cancer
Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany. European Journal of Nuclear Medicine
(Impact Factor: 5.38).
12/2006; 33(12):1426-31. DOI: 10.1007/s00259-006-0175-6
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.
Available from: Andreas Kjaer
- "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      . "
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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.
Available from: Jeho Jeong
- "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. "
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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.
Available from: PubMed Central
- "Our recent preliminary study also revealed that the maximum standardized uptake value (SUVmax) of PET/CT in the cervical lymph nodes predicted cervical metastasis of a carcinoma from an unknown primary tumor (3). There is certain controversy, however, as certain studies did not find any association between FDG uptake and the hypoxic status of specific carcinomas (21,22). The expression of HIF-1α and the correlated target genes, including Glut-1, is regulated by the PI3K/protein kinase B (Akt) pathway (23,24). "
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ABSTRACT: High fluorodeoxyglucose (FDG) uptake by human carcinomas, including head and neck cancers, is associated with a poor prognosis. Glucose transporter-1 (Glut-1) is believed to be an intrinsic marker of hypoxia in malignant tumors. The expression of hypoxia-inducible factor-1α (HIF-1α) and correlated target genes, including Glut-1, is regulated by the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. However, it remains unclear whether the PI3K/Akt signaling pathway is involved in regulating FDG uptake directly. In the present study, 24 consecutive patients with laryngeal carcinoma were examined pre-operatively and the standardized uptake values (SUV) of the laryngeal carcinomas were determined. Glut-1, HIF-1α, PI3K and phosphorylated-Akt (p-Akt) expression was detected by immunohistochemical staining of paraffin sections from the tumor specimens. Associations among SUVmax, Glut-1, HIF-1α, PI3K and p-Akt protein expression and the other clinical parameters were analyzed. The univariate analyses revealed a significantly shorter survival time along with higher HIF-1α (P=0.018) and PI3K (P=0.008) expression, but the survival time was not significantly correlated with Glut-1 or p-Akt expression. The multivariate analysis demonstrated that higher SUVmax (P=0.043) and PI3K expression (P=0.012) were significantly correlated with a poor survival time. Spearman's rank analysis showed significant correlations between SUVmax and HIF-1α (r=0.577; P=0.003), PI3K (r=1.0; P<0.0001) and p-Akt (r=0.577; P=0.003) expression. PI3K was associated with poorly- and moderately-differentiated laryngeal carcinoma (P=0.012). In conclusion, a high SUVmax indicates a poor prognosis for laryngeal carcinoma. Also, a high SUVmax may be associated with the increased expression of Glut-1, HIF-1α, PI3K and p-Akt.
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