Nimg-79. Early Treatment Response Assessment Using O-(2-18f-Fluoroethyl)-L-Tyrosine (Fet) Pet Compared to Mri in Malignant Gliomas Treated With Adjuvant Temozolomide Chemotherapy

Ceccon, Garry; Lohmann, Philipp; Tscherpel, Caroline; Dunkl, Veronika; Rapp, Marion; Stoffels, Gabriele; Herrlinger, Ulrich; Rosen, Jurij; Wollring, Michael; Shah, Nadim Joni; Fink, Gereon R.; Langen, Karl‐Josef; Galldiks, Norbert

doi:10.1093/neuonc/noy148.801

Cited by 2 publications

(19 citation statements)

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“…For univariate analysis of 13 C spectra and of 1 H MRS peaks identified as contributing to class discrimination, spectra were analyzed using Mnova7.1.0. Metabolites of interest were integrated, corrected for saturation and NOE, normalized to TSP and cell number, and samples compared using a Student t test.…”

Section: Mrs Data Analysismentioning

confidence: 99%

“…[2-13 C]pyruvate and [1- 13 C]aKG (Sigma-Aldrich) were polarized using a Hypersense DNP polarizer (Oxford) as described previously (19,20). For hyperpolarized [2-13 C]pyruvate, metabolism was investigated in live cells encapsulated in agarose beads using an MR-compatible perfusion systems into which 1.5 mL of hyperpolarized [2- 13 C]pyruvate mixed in Tris-based isotonic buffer was injected to a final concentration of 5 mmol/L as described previously (20). Data were acquired (depending on scanner availability) on either 500 MHz Agilent or 600 MHz Bruker spectrometer using 5 flip angle and 3s TR over 300s.…”

Section: Hyperpolarized 13 C Mrs Studiesmentioning

confidence: 99%

“…However, imaging studies to detect response to temozolomide prior to LGG tumor shrinkage have been limited. In GBM, one study used amide proton transfer imaging and detected response prior to tumor shrinkage in an animal model (12) and a preliminary clinical study reported on the utility of O-(2-18F-fluoroethyl)-Ltyrosine PET for early detection of response to temozolomide (13). In LGG, two clinical studies investigated the effects of temozolomide using 1 H magnetic resonance spectroscopy (MRS), a metabolic imaging method that reports on steady-state metabolite levels.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously used 1 H MRS to study mutant IDH1 glioma and showed that in addition to elevated levels of 2-hydroxyglutarate (2-HG), these cells have lower glutamate, lactate, and phosphocholine when compared with wild-type IDH1 cells (16). We also investigated mutant IDH1 glioma using another translational metabolic imaging method, namely hyperpolarized 13 C MRS, which provides complementary information by probing metabolic fluxes (17,18). Using this method, we showed that mutant IDH1 cells have a lower flux to glutamate from both pyruvate and a-ketoglutarate (aKG; refs.…”

Section: Introductionmentioning

confidence: 99%

“…We investigated genetically engineered and patient-derived mutant IDH1 cell and animal models. We first investigated the effects of temozolomide on the global metabolic profile of our cells using 1 H MRS combined with chemometrics, and then probed specific metabolic pathways using thermal equilibrium 13 C MRS and hyperpolarized 13 C MRS. We found that across our models, response to temozolomide treatment was associated with an increase in 1 H MRS glutamate levels as well as an increase in glutamate production from glucose and glutamine, resulting in hyperpolarized 13 C MRSdetectable elevated flux from both pyruvate and aKG. Our findings might assist in early detection of tumor response to temozolomide and thus help improve personalized treatment strategies for LGG patients.…”

Section: Introductionmentioning

confidence: 99%

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Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment

et al. 2020

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◥Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models. Using 1 H MRS in combination with chemometrics identified several metabolic alterations in temozolomide-treated cells, including a significant increase in steady-state glutamate levels. This was confirmed in vivo, where the observed 1 H MRS increase in glutamate/ glutamine occurred prior to tumor shrinkage. Cells labeled with [1-13 C]glucose and [3-13 C]glutamine, the principal sources of cellular glutamate, showed that flux to glutamate both from glucose via the tricarboxylic acid cycle and from glutamine were increased following temozolomide treatment. In line with these results, hyperpolarized [5-13 C]glutamate produced from [2-13 C]pyruvate and hyperpolarized [1-13 C]glutamate produced from [1-13 C]a-ketoglutarate were significantly higher in temozolomide-treated cells compared with controls. Collectively, our findings identify 1 H MRS-detectable elevation of glutamate and hyperpolarized 13 C MRS-detectable glutamate production from either pyruvate or a-ketoglutarate as potential translatable metabolic biomarkers of response to temozolomide treatment in mutant IDH1 glioma.Significance: These findings show that glutamate can be used as a noninvasive, imageable metabolic marker for early assessment of tumor response to temozolomide, with the potential to improve treatment strategies for mutant IDH1 patients.

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Section: Mrs Data Analysismentioning

confidence: 99%

Section: Hyperpolarized 13 C Mrs Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment

et al. 2020

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Efficacy and Safety of Temozolomide Combined with Radiotherapy in the Treatment of Malignant Glioma

Wei

2022

Journal of Healthcare Engineering

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MG is a clinical common intracranial tumor, with the characteristics of strong invasion. In our study, we aim to explore the efficacy and safety of temozolomide combined with radiotherapy in the treatment of malignant glioma (MG) and its influence on postoperative complications and survival rate of patients. 120 MG patients admitted to our hospital (January 2019–January 2020) were chosen as the research objects and were randomly divided into group A (n = 60) and group B (n = 60). All patients were treated with radiotherapy, and patients in group A were additionally treated with temozolomide. The clinical efficacy, quality of life, incidence of adverse reactions, incidence of postoperative complications, survival rates, and average survival time of the two groups were compared. The objective remission rate (ORR), disease control rate (DCR), survival rates after one year and two years of follow-up, and the number of patients with improved quality of life in group A were markedly higher compared with group B P < 0.05 . The incidence of postoperative complications in group A was remarkably lower compared with group B P < 0.05 . The average survival time of group A was dramatically longer compared with group B P < 0.001 . There was no significant difference in the incidence of adverse reactions between the two groups P > 0.05 , and no new adverse reactions occurred in the patients. Temozolomide combined with radiotherapy can effectively improve the quality of life, treatment effect, and survival rate of MG patients, with a lower incidence of postoperative complications and better tolerance. Our finding indicates that temozolomide combined with radiotherapy has a high clinical application value. In addition, it indicates that this treatment method should be promoted in practice.

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Nimg-79. Early Treatment Response Assessment Using O-(2-18f-Fluoroethyl)-L-Tyrosine (Fet) Pet Compared to Mri in Malignant Gliomas Treated With Adjuvant Temozolomide Chemotherapy

Cited by 2 publications

References 0 publications

Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment

Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment

Efficacy and Safety of Temozolomide Combined with Radiotherapy in the Treatment of Malignant Glioma

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