pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

Gagel, Bernd; Piroth, Marc D.; Pinkawa, Michael; Reinartz, Patrick; Zimny, M.; Kaiser, Hartmut; Stanzel, S.; Asadpour, Branka; Demirel, Cengiz Bekir; Hamacher, Kurt; Coenen, Heinz H.; Scholbach, Thomas; Maneschi, Payam; DiMartino, Ercole; Eble, Michael J.

doi:10.1186/1471-2407-7-113

Cited by 68 publications

(48 citation statements)

References 30 publications

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“…Quantifying the relationship between tumor oxygenation and vascular functions has a profound impact on preclinical and clinical cancer research. A positive correlation between pO 2 from polarographic measurements and blood perfusion was shown in patients with head and neck SCC (23). Although tumor oxygenation status correlates with regional blood perfusion levels, the contribution of highly leaky neo-vasculature to tumor oxygen level remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Matsumoto¹,

Yasui²,

Karmakar

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Architectural and functional abnormalities of blood vessels are a common feature in tumors. A consequence of increased vascular permeability and concomitant aberrant blood flow is poor delivery of oxygen and drugs, which is associated with treatment resistance. In the present study, we describe a strategy to simultaneously visualize tissue oxygen concentration and microvascular permeability by using a hyperpolarized 1 H-MRI, known as Overhauser enhanced MRI (OMRI), and an oxygen-sensitive contrast agent OX63. Substantial MRI signal enhancement was induced by dynamic nuclear polarization (DNP). The DNP achieved up to a 7,000% increase in MRI signal at an OX63 concentration of 1.5 mM compared with that under thermal equilibrium state. The extent of hyperpolarization is influenced mainly by the local concentration of OX63 and inversely by the tissue oxygen level. By collecting dynamic OMRI images at different hyperpolarization levels, local oxygen concentration and microvascular permeability of OX63 can be simultaneously determined. Application of this modality to murine tumors revealed that tumor regions with high vascular permeability were spatio-temporally coincident with hypoxia. Quantitative analysis of image data from individual animals showed an inverse correlation between tumor vascular leakage and median oxygen concentration. Immunohistochemical analyses of tumor tissues obtained from the same animals after OMRI experiments demonstrated that lack of integrity in tumor blood vessels was associated with increased tumor microvascular permeability. This dual imaging technique may be useful for the longitudinal assessment of changes in tumor vascular function and oxygenation in response to chemotherapy, radiotherapy, or antiangiogenic treatment.angiogenesis ͉ dynamic nuclear polarization ͉ hyperpolarized MRI ͉ tumor hypoxia ͉ DCE-MRI

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Section: Discussionmentioning

confidence: 99%

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Matsumoto¹,

Yasui²,

Karmakar

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Bentzen et al [195] , Rasey et al [196] , Bentzen et al [197] , Troost et al [198] Bentzen et al [125] , Gagel et al [126] , Bruehlmeier et al [199] , Lawrentschuk et al [200] , O'Donoghue et al [72] , Piert et al [166] , Sørensen et al [201] , Gagel et al [202] , Carlin et al [203] , Chang et al [204] , Mortensen et al [127] Hatano et al [205] , Huang et al [206] , Huang et al [207] , Oehler et al [208] , Cho et al [209] , Troost et al [210] , Matsumoto et al [136] , Troost et al [198] , Dubois et al [211] Dubois et al [211] , Cherk et al [212] , Riesterer et al [213] , Lehmann et al [214] , Chen et al [215] , Campanile et al [216] , Cheng et al [217] , Sato et al [218] , Norikane et al [219] Cherk et al [212] , Eschmann et al [77] , Gagel et al [82] , Koh et al [87] , Rasey et al [220] , Vera et al…”

Section: F]fmisomentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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Core tip:This review provides an overview of the current applications of positron emission tomography for hypoxia and perfusion imaging in lung cancer. Available PET tracers are discussed and the benefits of combined hypoxia and perfusion PET imaging are clarified. Hypoxia imaging could aid in selecting patients for hypoxia-specific treatment strategies. To achieve this, consensus about the optimal imaging protocol and quantification method is essential. Large clinical trials are needed to confirm the value of hypoxia imaging for improving patient care.Verwer EE, Boellaard R, van der Veldt AAM. Positron emission tomography to assess hypoxia and perfusion in lung cancer.

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“…Oxygen probe measurements have previously been applied to compare the uptake of PET tracers to average tumor pO 2 values (35)(36)(37). Moreover, the technique has also been used for evaluation of the spatial distribution of hypoxia PET tracers in a few studies (21,38,39).…”

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confidence: 99%

⁶⁴Cu-ATSM Reflects pO₂ Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with ⁶⁴CuCl₂

Jørgensen

Forman

et al. 2015

J Nucl Med

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The hypoxia PET tracer 64 Cu-diacetyl-bis(N 4 -methylthiosemicarbazonate) ( 64 Cu-ATSM) has shown promising results in clinical studies. However, concerns have been raised with regard to the possible effect of copper metabolism and free copper on tumor uptake and thereby the robustness of 64 Cu-ATSM as a hypoxia marker. In this study, accumulation and distribution of 64 Cu-ATSM and 64 CuCl 2 in tumor tissue were compared with partial pressure of oxygen (pO 2 ) probe measurements. Methods: One-hour dynamic PET scans were performed on nude mice bearing subcutaneous human head and neck tumors (FaDu) and human colorectal tumors (HT29) after administration of either 64 Cu-ATSM or 64 CuCl 2 . Subsequently, tracks were generated and track markers were positioned in tumors to allow for registration of their exact location on the high-resolution CT scan. After completion of the CT scan, pO 2 probe measurements were performed along each track. PET and CT images were coregistered and ROIs drawn on the basis of the location of track markers and pO 2 probe measurement depth. A linear mixed model for repeated measures was applied for the comparison of PET tracer uptake to corresponding pO 2 values. Results: Comparable uptake of 64 Cu-ATSM and 64 CuCl 2 was found in the kidney, muscle, and liver of all animals, but 64 CuCl 2 showed a higher uptake 10-60 min after injection in both tumor models. Significant differences were also found for both tumor-to-muscle and tumor-to-liver ratios. The intratumoral distribution of 64 Cu-ATSM, but not 64 CuCl 2 , showed a significant negative relationship with pO 2 measurements in FaDu tumors. However, this relationship was not found in HT29 tumors. Conclusion: 64 Cu-ATSM and 64 CuCl 2 displayed different uptake in tumors. In human head and neck xenografts, 64 Cu-ATSM but not 64 CuCl 2 reflected pO 2 measurements, indicating that 64 Cu-ATSM is a hypoxia-specific marker in this tumor type. However, data from colorectal cancer xenografts indicated that 64 Cu-ATSM may not be a hypoxia marker in all tumor types.

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pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

Cited by 68 publications

References 30 publications

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Positron emission tomography to assess hypoxia and perfusion in lung cancer

⁶⁴Cu-ATSM Reflects pO₂ Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with ⁶⁴CuCl₂

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pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

Cited by 68 publications

References 30 publications

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI

Positron emission tomography to assess hypoxia and perfusion in lung cancer

64Cu-ATSM Reflects pO2 Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with 64CuCl2

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⁶⁴Cu-ATSM Reflects pO₂ Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with ⁶⁴CuCl₂