Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR2* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

Baker, Lauren C.J.; Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley; Walker‐Samuel, Simon; Burrell, Jake S.; Ashcroft, Margaret; Howe, Franklyn A.; Griffiths, John R.; Raleigh, James A.; Kogel, Albert J. van der; Robinson, Simon P.

doi:10.1016/j.ijrobp.2013.04.051

Cited by 15 publications

(20 citation statements)

References 24 publications

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“…A double hypoxia marker approach [28, 47] was used to verify tumor reoxygenation. Immediately after OE-MRI, three tumor bearing rats, while breathing oxygen, were injected intravenously with pimonidazole as a baseline tumor hypoxia marker.…”

Section: Methodsmentioning

confidence: 99%

“…Analogous use of immunochemistry of nitroimidazole trapping has allowed pulse chase evaluation of hypoxia modulation, but requires biopsy [28]. …”

Section: Introductionmentioning

confidence: 99%

“…The tissue water proton apparent transverse relaxation rate (R 2 *) is strongly influenced by the concentration of deoxyhemoglobin, which is paramagnetic [2, 28]. This provides blood oxygen level dependent (BOLD) contrast, which is the basis of fMRI used in studies of neuronal activation.…”

Section: Introductionmentioning

confidence: 99%

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Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

White

Zhang

et al. 2016

Cancer Letters

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Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) techniques were evaluated as potential non-invasive predictive biomarkers of radiation response. Semi quantitative blood-oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) contrast, and quantitative responses of relaxation rates (ΔR1 and ΔR2*) to an oxygen breathing challenge during hypofractionated radiotherapy were applied. OE-MRI was performed on subcutaneous Dunning R3327-AT1 rat prostate tumors (n = 25) at 4.7 T prior to each irradiation (2Fx15 Gy) to the gross tumor volume. Response to radiation, while inhaling air or oxygen, was assessed by tumor growth delay measured up to four times the initial irradiated tumor volume (VQT). Radiation-induced hypoxia changes were confirmed using a double hypoxia marker assay. Inhaling oxygen during hypofractionated radiotherapy significantly improved radiation response. A correlation was observed between the difference in the 2nd and 1st ΔR1 (ΔΔR1) and VQT for air breathing rats. The TOLD response before the 2nd fraction showed a moderate correlation with VQT for oxygen breathing rats. The correlations indicate useful prognostic factors to predict tumor response to hypofractionation and could readily be applied for patient stratification and personalized radiotherapy treatment planning.

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Section: Methodsmentioning

confidence: 99%

“…Analogous use of immunochemistry of nitroimidazole trapping has allowed pulse chase evaluation of hypoxia modulation, but requires biopsy [28]. …”

Section: Introductionmentioning

confidence: 99%

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Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

White

Zhang

et al. 2016

Cancer Letters

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“…Hypoxic challenges were performed by the injection of the antivascular agent CA4, described to induce a vascular shutdown as early as 3 hours after the administration of the drug (36), whereas hypoxic challenges were induced by a carbogen breathing (95%O 2 /5%CO 2 ) known to acutely increase tumor oxygenation in a wide range of tumor models/xenografts and in human tumors (36)(37)(38)(39)(40)31). Oxygenation was assessed in matching tumors (the same tumors underwent both EPR and MRI experiments) using EPR oximetry as a method of reference for the quantitative assessment of the tumor pO 2 .…”

Section: Introductionmentioning

confidence: 99%

Qualification of a Noninvasive Magnetic Resonance Imaging Biomarker to Assess Tumor Oxygenation

Colliez

Neveu

Magat

et al. 2014

Clinical Cancer Research

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Purpose: Although hypoxia has been long recognized as a crucial factor impairing tumor response in many therapeutic schemes, atraumatic and reliable methods of individually quantifying tumor oxygenation are still lacking in day-to-day clinical practice. The aim of this work was to investigate the potentially quantitative properties of our recently described noninvasive magnetic resonance (MR) technique "MOBILE" (mapping of oxygen by imaging lipids relaxation enhancement) and to qualify this endogenous contrast as a tumor hypoxia marker.Experimental Design: The "MOBILE" technique, which assesses the longitudinal MR relaxation rate, R 1 , of lipid protons, was benchmarked with the parent technique which assesses the global (or water) R 1 , in response to a hyperoxic challenge (carbogen breathing) and to a hypoxic challenge (combretastatin A4) in MDA-MB-231 xenografts and in NT2 mammary tumors. Electron paramagnetic resonance (EPR) oximetry was used to quantitatively assess the tumor pO 2 in matching tumors longitudinally.Results and Conclusion: Our study evidenced that (i) positive and negative changes in tumor oxygenation can be detected using MOBILE; (ii) a change in the R 1 of lipids is positively correlated with a change in the tumor pO 2 (P ¼ 0.0217, r ¼ 0.5097); (iii) measured lipid R 1 values are positively correlated with absolute pO 2 values in both tumor models (P ¼ 0.0275, r ¼ 0.3726); and (iv) changes in the R 1 of lipids are more sensitive than changes in the global R 1 . As this technique presents unique translational properties, it seems promising for the individual longitudinal monitoring of tumor oxygenation in a clinical setting.

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“…Unlike the polarographic device, the magnitude of the measured signal is inversely related to the oxygen present, so the signal to noise increases at low concentrations, this is especially useful when measuring oxygen in hypoxic tissues (tumors). 113 …”

Section: 4 Oxygenmentioning

confidence: 99%

A review of flux considerations for in vivo neurochemical measurements

Paul

Stenken

2015

Analyst

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The mass transport or flux of neurochemicals in the brain and how this flux affects chemical measurements and their interpretation is reviewed. For all endogenous neurochemicals found in the brain, the flux of each of these neurochemicals exists between sources that produce them and the sites that consume them all within μm distances. Principles of convective-diffusion are reviewed with a significant emphasis on the tortuous paths and discrete point sources and sinks. The fundamentals of the primary methods of detection, microelectrodes and microdialysis sampling of brain neurochemicals are included in the review. Special attention is paid to the change in the natural flux of the neurochemicals caused by implantation and consumption at microelectrodes and uptake by microdialysis. The detection of oxygen, nitric oxide, glucose, lactate, and glutamate, and catecholamines by both methods are examined and where possible the two techniques (electrochemical vs. microdialysis) are compared. Non-invasive imaging methods: magnetic resonance, isotopic fluorine MRI, electron paramagnetic resonance, and positron emission tomography are also used for different measurements of the above-mentioned solutes and these are briefly reviewed. Although more sophisticated, the imaging techniques are unable to track neurochemical flux on short time scales, and lack spatial resolution. Where possible, determinations of flux using imaging are compared to the more classical techniques of microdialysis and microelectrodes.

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Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR2* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

Cited by 15 publications

References 24 publications

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

Qualification of a Noninvasive Magnetic Resonance Imaging Biomarker to Assess Tumor Oxygenation

A review of flux considerations for in vivo neurochemical measurements

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