Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy

Arbeit, Jeffrey M.; Brown, J. Martin; Chao, K.S. Clifford; Chapman, J. D.; Eckelman, William C.; Fyles, Anthony; Giaccia, Amato J.; Hill, Richard P.; Koch, Cameron J.; Krishna, Murali C.; Krohn, Kenneth A.; Lewis, Jason S.; Mason, Ralph P.; Melillo, Giovanni; Padhani, Anwar R.; Powis, Garth; Rajendran, Joseph G.; Reba, Richard C.; Robinson, Simon P.; Semenza, Gregg L.; Swartz, Harold M.; Vaupel, Peter; Yang, David J.; Tatum, James L.

doi:10.1080/09553000601002324

Cited by 541 publications

(494 citation statements)

References 263 publications

Supporting

Mentioning

485

Contrasting

Unclassified

Order By: Relevance

“…Hypoxia can render tumor cells up to three times more resistant to radiation relative to aerobic cells (7). Hypoxia has been shown in several studies to be an important determinant of locoregional control (LRC) and overall survival in many tumors, including head and neck cancer (HNC) (2,(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Lee

Mechalakos

Nehmeh

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

208

157

View full text Add to dashboard Cite

Purpose-Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV h ) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV h increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ( 18 F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.Methods and Materials-18 F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and 18 F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated 18 F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate 18 F-FMISO PET/CT-guided IMRT plans.Results-The heterogeneous distribution of 18 F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing 18 F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV h and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV h for 2 patients and were successful in 1, with normal tissue sparing. Conclusion-It was feasible to dose escalate the GTV h to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Furthermore, its use requires a skilled operator, and it is invasive, subject to sampling errors, and unable to exclude low readings obtained from nonviable necrotic tissue (2,4,(12)(13)(14)(15)(16)(17). Other methods have claimed equivalent accuracy (e.g., the Comet assay) (18).…”

Section: Introductionmentioning

confidence: 99%

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Lee

Mechalakos

Nehmeh

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

208

157

View full text Add to dashboard Cite

show abstract

“…Measurements of the hypoxic fraction of tumors before and during radiation therapy may be useful for identifying patients who may respond poorly to conventional radiation treatment and, therefore, may benefit from a more aggressive treatment regimen. Various techniques for measuring tumor hypoxia have been used, but at present no 'gold standard' exists for assessing the fraction of hypoxic tissue in human tumors (9).…”

mentioning

confidence: 99%

“…Gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested to be a useful noninvasive method for characterizing the physiological microenvironment of tumors (9). The uptake of Gd-DTPA in tumors depends on several microenvironmental parameters related to the oxygenation status of the tissue, including blood perfusion, vascular density, vessel wall permeability, cell density, and extracellular volume fraction (10).…”

mentioning

confidence: 99%

Limitations of dynamic contrast‐enhanced MRI in monitoring radiation‐induced changes in the fraction of radiobiologically hypoxic cells in human melanoma xenografts

Benjaminsen

Melås

Mathiesen

et al. 2008

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Purpose:To investigate the potential of gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting radiation-induced changes in the fraction of radiobiologically hypoxic cells in A-07 human melanoma xenografts. Materials and Methods:A-07 tumors were randomly assigned to an unirradiated control group or a group given a single radiation dose of 20 Gy. DCE-MRI and measurement of fraction of hypoxic cells were performed immediately before and 24 h after the radiation exposure. Tumor images of E ⅐ F (E is the initial extraction fraction of Gd-DTPA and F is blood perfusion) and ( is proportional to extracellular volume fraction) were produced by subjecting DCE-MRI series to Kety analysis. Fraction of hypoxic cells was measured by using a radiobiological assay based on the paired survival curve method.Results: Fraction of radiobiologically hypoxic cells was higher in irradiated tumors (26.2 Ϯ 5.8%) than in unirradiated tumors (7.5 Ϯ 2.7%) by a factor of 3.5 Ϯ 1.5 (P ϭ 0.0093), whereas only minor radiation-induced changes in E ⅐ F and could be detected.Conclusion: DCE-MRI does not seem to offer insight into the changes in fraction of radiobiologically hypoxic cells occurring in A-07 tumors within 24 h after irradiation with 20 Gy.

show abstract

“…of !the decreased oxygen tensions by switching from aerobic to anaerobic metabolism. This metabolic switch is mediated by hypoxia-inducible factor (HIF) [27][28][29][30][31], transcription factors which regulate the expression of genes related to cancer cell survival such as glycolysis, angiogenesis, and invasion/metastasis [27,[32][33][34]. Cells that adjust to these hypoxic conditions in a tumor have also been associated with the ability to resist both chemotherapy and radiotherapy [19,22,[34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system

et al. 2016

View full text Add to dashboard Cite

(100-200 word limit)This work demonstrates the application of a 3D culture system, which is known as Cells-in-Gels-in-Paper or CiGiP, in evaluating the response of lung cancer cells to ionizing radiation. This system has four attributes: (i) multiple layers of paper, containing cell-embedded hydrogels, are assembled into a stack to form a thick (~800 µm) tissue-like construct, (ii) the metabolism of the cells, coupled with the boundary conditions imposed by an impermeable holder, generate a gradient of oxygen and nutrients that decreases monotonically in the stack, (iii) the construct has no peripheral components (e.g., pumps, tubing), that fits easily in an irradiator, and (iv) the construct can be disassembled into individual layers, allowing for the quantification of cellular phenotypes based on their position within the stack. With increased distance from the source of oxygenated media, cells show increased levels of hypoxia-inducible factor, decreased proliferation, and reduced sensitivity to ionizing radiation. The multi-layer culture setup for CiGiP also distinguished differences in the radiosensitivity of three isogenic variants of A549 cancer cells, which have known differences in their metastatic behavior in vivo. The CiGiP system can, therefore, capture aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon inaccessible in traditional culture systems.

show abstract

Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy

Cited by 541 publications

References 263 publications

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Limitations of dynamic contrast‐enhanced MRI in monitoring radiation‐induced changes in the fraction of radiobiologically hypoxic cells in human melanoma xenografts

Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system

Contact Info

Product

Resources

About