ArticlePloS one2014
Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Implementation of a Multicenter Biobanking Collaboration for Next-Generation Sequencing-Based Biomarker Discovery Based on Fresh Frozen Pretreatment Tumor Tissue Biopsies.The oncologist · 2017Trial
- Metabolic targeting of regulatory T cells in oral squamous cell carcinoma: new horizons in immunotherapy.Molecular cancer · 2024Review
- 3D convolutional neural networks predict cellular metabolic pathway use from fluorescence lifetime decay data.APL bioengineering · 2024Article
- Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data.Cancer cell international · 2023Article
- Intrinsic radiomic expression patterns after 20 Gy demonstrate early metabolic response of oropharyngeal cancers.Medical physics · 2021Article
- Review
- Increased formation of reactive oxygen species during tumor growth: Ex vivo low-temperature EPR and in vivo bioluminescence analyses.Free radical biology & medicine · 2020Article
- Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients.Lab on a chip · 2019Article
- Changing landscape of optical imaging in skeletal metastases.Journal of bone oncology · 2019Review
- Transporter and protease mediated delivery of platinum complexes for precision oncology.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Review
- Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer.PloS one · 2019Article
- Visualizing the effects of metformin on tumor growth, vascularity, and metabolism in head and neck cancer.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2018Article
- Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation.PloS one · 2017Article
- Prognostic significance of monocarboxylate transporter expression in oral cavity tumors.Cell cycle (Georgetown, Tex.) · 2016Article
- More challenges ahead-metabolic heterogeneity of pancreatic cancer stem cells.Molecular & cellular oncology · 2016Article
- A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images.PloS one · 2016Article
- Simulating Heterogeneous Tumor Cell Populations.PloS one · 2016Article
- Mitochondrial targeted β-lapachone induces mitochondrial dysfunction and catastrophic vacuolization in cancer cells.Bioorganic & medicinal chemistry letters · 2015Article
- Frequently asked questions in hypoxia research.Hypoxia (Auckland, N.Z.) · 2015Review
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9 authors.
Funding
Abstract
purposeIntratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC) xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor. EXPERIMENTAL
designCal33 cells were grown as xenograft tumors (n = 16) in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG) concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in clinical PET scans.
resultsIR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001). IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18)F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.
conclusionHypoxia is associated with increased intratumoral metabolic heterogeneity. (18)F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.
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