Monitoring Combretastatin A4–induced tumor hypoxia and hemodynamic changes using endogenous MR contrast and DCE‐MRI

Colliez, Florence; Fruytier, Anne‐Catherine; Magat, Julie; Neveu, Marie‐Aline; Cani, Patrice D.; Gallez, Bernard; Jordan, Bénédicte F.

doi:10.1002/mrm.25642

Cited by 18 publications

(20 citation statements)

References 36 publications

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“…The fact that the width of EPR resonance line correlates with oxygen tension has been used in a variety of biological applications. [15][16][17][18][19][20][21][22][23][24][25][26] To perform repeated measurements of tissue pO 2 in humans, we have developed a novel class of implantable sensors using stable paramagnetic molecules or crystals embedded in biocompatible polymers. [27][28][29][30][31] Recently, we have also started using EPR oximetry with an implantable sensor, called OxyChip, for measuring tumor oxygen levels in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film

Kmiec

Hou

Kuppusamy

et al. 2018

Magnetic Resonance in Med

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Purpose Transcutaneous oxygen tension (TcpO2) provides information about blood perfusion in the tissue immediately below the skin. These data are valuable in assessing wound healing problems, diagnosing peripheral vascular/arterial insufficiency, and predicting disease progression or the response to therapy. Currently, TcpO2 is primarily measured using electrochemical skin sensors, which consume oxygen and are prone to calibration errors. The goal of the present study was to develop a reliable method for TcpO2 measurement in human subjects. Methods We have developed a novel TcpO2 oximetry method based on electron paramagnetic resonance (EPR) principles with an oxygen‐sensing skin adhesive film, named the superficial perfusion oxygen tension (SPOT) chip. The SPOT chip is a 3‐mm diameter, 60‐μm thick circular film composed of a stable paramagnetic oxygen sensor. The chip is covered with an oxygen‐barrier material on one side and secured on the skin by a medical adhesive transfer tape to ensure that only the oxygen that diffuses through the skin surface is measured. The method quantifies TcpO2 through the linewidth of the EPR spectrum. Results Repeated measurements using a cohort of 10 healthy human subjects showed that the TcpO2 measurements were robust, reliable, and reproducible. The TcpO2 values ranged from 7.8 ± 0.8 to 22.0 ± 1.0 mmHg in the volar forearm skin (N = 29) and 8.1 ± 0.3 to 23.4 ± 1.3 mmHg in the foot (N = 86). Conclusions The results demonstrated that the SPOT chip can measure TcpO2 reliably and repeatedly under ambient conditions. The SPOT chip method could potentially be used to monitor TcpO2 in the clinic.

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Section: Introductionmentioning

confidence: 99%

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film

Kmiec

Hou

Kuppusamy

et al. 2018

Magnetic Resonance in Med

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“…(9, 15, 16) We conducted a multicenter, Phase II study to determine if 18 F-FMISO PET and MRI could measure tumor hypoxia and changes in tumor vasculature in order to predict survival in patients with newly diagnosed GBM. The primary aim was to determine the association of baseline hypoxia, as measured by 18 F-FMISO PET, and vascular parameters, as measured by DSC/DCE MRI with overall survival.…”

Section: Introductionmentioning

confidence: 99%

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI

Gerstner

Zhang

Fink

et al. 2016

Clinical Cancer Research

105

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Purpose Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma (GBM). Experimental Design Prior to start of chemoradiation, GBM patients underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression free and overall survival. Results Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pre-treatment 18F-FMISO SUVpeak (p=0.048), mean ktrans (p=0.024), and median ktrans (p=0.045) were significantly associated with shorter overall survival. Higher pre-treatment median ktrans (p=0.021), normalized RCBV (p=0.0096), and nCBF (p=0.038) were significantly associated with shorter progression free survival. SUVpeak (AUC = 0.75, 95%CI 0.59 to 0.91), nRCBV (AUC=0.72, 95% CI0.56–0.89) and nCBF (AUC = 0.72, 95%CI 0.56 to 0.89) were predictive of survival at 1 year. Conclusions Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed GBM patients and these important physiological markers can be measured safely and reliably using MRI and 18F-FMISO PET.

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“…An imbalance in oxygen demand and supply supposedly occurs in highly proliferative tumors, leading to hypoxic conditions MAJOR PAPER dynamic susceptibility contrast (DSC) or dynamic contrastenhanced (DCE) MRI perfusion techniques. [9][10][11][12][13] Blood flow and blood volume are quantified by DSC. Blood volume and vascular permeability are quantified by DCE as V p and K trans , respectively.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and <sup>18</sup>F-Fluorodeoxyglucose Accumulation Data

Shimizu

Kudo²,

Kameda

et al. 2020

magn reson med sci

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Purpose:The aim of this study was to generate a multivariate model using various MRI markers of blood flow and vascular permeability and accumulation of 18 F-fluorodeoxyglucose (FDG) to predict the extent of hypoxia in an 18 F-fluoromisonidazole (FMISO)-positive region.Methods: Fifteen patients aged 27-74 years with brain tumors (glioma, n = 13; lymphoma, n = 1; germinoma, n = 1) were included. MRI scans were performed using a 3T scanner, and dynamic contrast-enhanced (DCE) perfusion and arterial spin labeling images were obtained. K trans and V p maps were generated using the DCE images. FDG and FMISO positron emission tomography scans were also obtained. A model for predicting FMISO positivity was generated on a voxel-by-voxel basis by a multivariate logistic regression model using all the MRI parameters with and without FDG. Receiver-operating characteristic curve analysis was used to detect FMISO positivity with multivariate and univariate analysis of each parameter. Cross-validation was performed using the leave-one-out method. Results:The area under the curve (AUC) was highest for the multivariate prediction model with FDG (0.892) followed by the multivariate model without FDG and univariate analysis with FDG and K trans (0.844 for all). In cross-validation, the multivariate model with FDG had the highest AUC (0.857 ± 0.08) followed by the multivariate model without FDG (0.834 ± 0.119). Conclusion:A multivariate prediction model created using blood flow, vascular permeability, and glycometabolism parameters can predict the extent of hypoxia in FMISO-positive areas in patients with brain tumors.

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Monitoring Combretastatin A4–induced tumor hypoxia and hemodynamic changes using endogenous MR contrast and DCE‐MRI

Abstract: MOBILE was identified as a marker to follow a decrease in oxygenation induced by CA4. However, DCE-MRI showed a higher dynamic range to follow changes in tumor hemodynamics induced by CA4.

Cited by 18 publications

References 36 publications

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI

Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and <sup>18</sup>F-Fluorodeoxyglucose Accumulation Data

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