The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET

Liu, Feng-Min; Gao, Yufei; Kong, Yanyan; Guan, Yihui; Zhang, Jinsen; Li, Shuai-Hong; Ye, Dan; Wen, Wenyu; Zuo, Chuantao; Hua, Wei

doi:10.1186/s12885-021-07797-6

Cited by 9 publications

(9 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, glucose metabolism as assessed by FDG PET in IDH -wildtype tumors tended to be higher than that in IDH -mutant tumors in the present study, but the difference did not reach statistical significance. This result was not in agreement with previous studies, in which the FDG uptake of IDH -wildtype tumors was significantly higher than that of IDH -mutant tumors [ 13 – 15 ]. This could be because the previous studies included all grades of diffuse gliomas (WHO grade II–IV), but the present study examined FDG PET only in malignant tumors (WHO grade III and IV).…”

Section: Discussioncontrasting

confidence: 99%

“…A recent study showed that IDH -mutant cells shift glucose metabolism from glycolysis to the TCA cycle [ 11 , 12 ]. In addition, several clinical studies demonstrated that the glucose uptake of IDH -mutant gliomas was significantly lower than that of IDH -wildtype gliomas [ 13 – 15 ]. Recently, an exploratory study using oxygen-sensitive molecular MRI revealed that IDH -mutant gliomas exhibit lower hypoxia and acidity compared with IDH -wildtype gliomas [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas

et al. 2021

View full text Add to dashboard Cite

Background Tumor hypoxia and glycolysis have been recognized as determinant factors characterizing tumor aggressiveness in malignant gliomas. To clarify in vivo hypoxia and glucose metabolism in relation to isocitrate dehydrogenase (IDH) mutation and chromosome 1p and 19q (1p/19q) codeletion status, we retrospectively analyzed hypoxia as assessed by positron emission tomography (PET) with [18F]-fluoromisonidazole (FMISO) and glucose metabolism as assessed by PET with [18F]-fluoro-2-deoxy-d-glucose (FDG) in newly diagnosed malignant gliomas. Methods In total, 87 patients with newly diagnosed supratentorial malignant (WHO grade III and IV) gliomas were enrolled in this study. They underwent PET studies with FMISO and FDG before surgery. The molecular features and histopathological diagnoses based on the 2016 WHO classification were determined using surgical specimens. Maximal tumor-to-normal ratio (TNR) was calculated for FDG PET, and maximal tumor-to-blood SUV ratio (TBR) was calculated for FMISO PET. The PET uptake values in relation to IDH mutation and 1p/19q codeletion status were statistically analyzed. Results In all tumors and malignant astrocytomas, the median FMISO TBR in IDH-wildtype tumors was significantly higher than that in IDH-mutant tumors (P < 0.001 and P < 0.01, respectively). In receiver operating characteristic (ROC) analysis, the area under the curve showed that the sensitivity for the discrimination was moderate (0.7–0.8) and the specificity was low (0.65–0.68). In the same population, the median FDG TNR in IDH-wildtype tumors tended to be higher than that in IDH-mutant tumors, but the difference was not statistically significant. In WHO grade III anaplastic astrocytomas, there were no significant differences in median FMISO TBR or FDG TNR between IDH-mutant and IDH-wildtype tumors. In IDH-mutant WHO grade III anaplastic gliomas, there were no significant differences in median FMISO TBR or FDG TNR between anaplastic astrocytomas and anaplastic oligodendrogliomas. Conclusions Tumor hypoxia as assessed by FMISO PET was informative for prediction of the IDH mutation status in newly diagnosed malignant gliomas. However, the accuracy of the discrimination was not satisfactory for clinical application. On the other hand, glucose metabolism as assessed by FDG PET could not differentiate the IDH-mutant status. Moreover, PET studies using FMISO and FDG could not predict IDH mutation and 1p/19q codeletion status in WHO grade III tumors.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Recent studies also show that IDH1-derived 2hydroxyglutarate can facilitate degradation of Hif1-α and thus reduce the Warburg-effect through down-regulation of multiple genes in the glycolytic pathway (113). Further evidence of an inhibitory effect of the IDH1 mutation on glucose consumption and glycolysis was obtained recently from PET analysis (116). The long-term survival of the patient could therefore result in part from a synergistic interaction between his self-directed KMT and the anti-cancer effects of the IDH1-R132H mutation.…”

Section: Discussionmentioning

confidence: 95%

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

et al. 2021

View full text Add to dashboard Cite

Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4–6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4).Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss.Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor.Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.

show abstract

“…In contrast to results observed for murine CT-2A glioma, recrystallized CHCA matrix in positive polarity mode was enriched for metabolites in pathways grouped as Carbohydrate Metabolism rather than Energy Metabolism. This is likely a reflection of the biology of decreased glucose uptake in IDH -mutant tumors compared to IDH -wildtype tumors, such as CT-2A glioma [26].…”

Section: Resultsmentioning

confidence: 99%

Matrix selection for the visualization of small molecules and lipids in brain tumors using untargeted MALDI-TOF mass spectrometry imaging

Lu,

Freytag,

Narayana

et al. 2023

Preprint

View full text Add to dashboard Cite

Matrix-assisted laser desorption/ionization mass spectrometry imaging allows the study of metabolic activity in the tumor microenvironment of brain cancers. The detectable metabolites within these tumors are contingent upon the choice of matrix, deposition technique, and polarity setting. In this study, we compared the performance of three different matrices, two deposition techniques, and use of positive and negative polarity in two different brain cancer types and across two species. Optimal combinations were confirmed by comparative analysis of lipid and small molecule abundance using liquid chromatography–mass spectrometry and RNA-sequencing assessing differential metabolites between normal and tumor regions. Our findings indicate that the recrystallized α cyano-4-hydroxycinnamic acid matrix in positive polarity offered superior performance for both detected metabolites and consistency with other techniques. Beyond these implications for brain cancer, our work establishes a workflow to identify optimal matrices for spatial metabolomics studies.

show abstract

The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET

Cited by 9 publications

References 43 publications

Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas

Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

Matrix selection for the visualization of small molecules and lipids in brain tumors using untargeted MALDI-TOF mass spectrometry imaging

Contact Info

Product

Resources

About