Physiologic characterisation of glioblastoma multiforme using MRI-based hypoxia mapping, chemical shift imaging, perfusion and diffusion maps

McMillan, Kathryn M.; Rogers, Baxter P.; Field, Aaron S.; Laird, Angela R.; Fine, Jason P.; Meyerand, M. Elizabeth

doi:10.1016/j.jocn.2005.12.025

Cited by 15 publications

(6 citation statements)

References 24 publications

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“…A bolus of gadolinium-based contrast agent is injected, and its distribution within the tissue of interest is analyzed through signal enhancement, thereby providing information on perfusion and permeability. This technique is regularly combined with oximetric methods such as PET imaging, blood oxygen level-dependent (BOLD)-MRI, or EPR oximetry to assess tumor hemodynamic parameters and their impact on therapy (75–77). Two parameters are regularly assessed by DCE-MRI, using the Tofts model: k trans , representing the volume transfer constant between blood plasma and extravascular extracellular space, and v p , defining the blood plasma volume per unit volume of tissue.…”

Section: Mri Methodsmentioning

confidence: 99%

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

2017

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Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses. However, the assessment of tumor oxygenation is not yet included in day-to-day clinical practice. This is due to the lack of a method for the quantitative and non-invasive mapping of tumor oxygenation. To fully integrate tumor hypoxia parameters into effective improvements of the individually tailored radiation therapy protocols in cancer patients, methods allowing non-invasively repeated, safe, and robust mapping of changes in tissue oxygenation are required. In this review, non-invasive methods dedicated to assessing tumor oxygenation with the ultimate goal of predicting outcome in radiation oncology are presented, including positron emission tomography used with nitroimidazole tracers, magnetic resonance methods using endogenous contrasts (R1 and R2*-based methods), and electron paramagnetic resonance oximetry; the goal is to highlight results of studies establishing correlations between tumor hypoxic status and patients’ outcome in the preclinical and clinical settings.

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Section: Mri Methodsmentioning

confidence: 99%

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

2017

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“…Patients with central nervous system (CNS) tumors were evaluated by MRI (magnetic resonance imaging) with gadolinium injected sequences (T1 and T2/FLAIR), DWI (diffusion-weighted imaging), perfusion sequences, and MR spectroscopy. Tumor response for those CNS tumors was based on Response Assessment in Neuro-Oncology (RANO) criteria [51,52]. The ADC (adherent diffusion coefficient) maps were retrospectively performed by two independent and experienced neuroradiologists.…”

Section: Tumor Responsementioning

confidence: 99%

SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers

Jannier¹,

Kemmel

Chammas

et al. 2020

Cancers

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Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Patients were enrolled according to a 3 + 3 escalation design with ten levels, aiming to determine the MTD (maximum tolerated dose) of rapamycin plus irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m2/day), associating biweekly intravenous irinotecan (125 to 240 mg/m2/dose). Toxicities, pharmacokinetics, efficacy analyses, and pharmacodynamics were evaluated. Forty-two patients, aged from 2 to 18 years, were included. No MTD was reached. Adverse events were mild to moderate. Only rapamycin doses of 1.5 mg/m2/day reached over time clinically active plasma concentrations. Tumor responses and prolonged stable disease were associated with a mean irinotecan area under the curve of more than 400 min.mg/L. Fourteen out of 31 (45.1%) patients had a non-progressive disease at 8 weeks. Most of them were sarcomas and brain tumors. For the phase II trial, we can then propose biweekly 125 mg/m2 irinotecan dose with a pharmacokinetic (PK) follow-up and a rapamycin dose of 1.5 mg/m2/day, reaching a blood concentration above 10 g/L.

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“…However, MRS is intrinsically versatile for in vivo metabolic imaging due to the NMR's ability to resolve protons or other nuclei in different chemical environments and therefore different metabolites (Brown 1992; Li, Negendank et al 1996; McMillan, Rogers et al 2006). For instance, MRS analysis of breast cancer has implicated a peak at 3.2 ppm as a biomarker for malignancy (Katz-Brull, Lavin et al 2002).…”

Section: Non-invasive Imaging Techniques To Monitor Metabolism Inmentioning

confidence: 99%

Stable isotope-resolved metabolomics and applications for drug development

Fan

Lorkiewicz

Sellers

et al. 2012

Pharmacology & Therapeutics

194

169

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Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality.

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Physiologic characterisation of glioblastoma multiforme using MRI-based hypoxia mapping, chemical shift imaging, perfusion and diffusion maps

Cited by 15 publications

References 24 publications

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

SFCE-RAPIRI Phase I Study of Rapamycin Plus Irinotecan: A New Way to Target Intra-Tumor Hypoxia in Pediatric Refractory Cancers

Stable isotope-resolved metabolomics and applications for drug development

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