nach oben

European Radiology

Erschienen in:

22.02.2022 | Molecular Imaging

MGMT promoter methylation status shows no effect on [¹⁸F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study

verfasst von: Shuangshuang Song, Yi Shan, Leiming Wang, Ye Cheng, Hongwei Yang, Guoguang Zhao, Zhenguang Wang, Jie Lu

Erschienen in: European Radiology | Ausgabe 8/2022

Einloggen, um Zugang zu erhalten

Abstract

Objectives

To investigate the effects of O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation status of gliomas on O-(2-¹⁸F-fluoroethyl)-L-tyrosine ([¹⁸F]FET) uptake and cerebral blood flow (CBF) of arterial spin labeling (ASL), evaluated by hybrid PET/MR. Stereotactic biopsy was used to validate the findings.

Methods

A set of whole tumor and reference volumes of interest (VOIs) based on PET/FLAIR imaging were delineated and transferred to the corresponding [¹⁸F]FET PET and CBF maps in 57 patients with newly diagnosed gliomas. The mean and max tumor-to-brain ratio (TBR) and normalized CBF (nCBF) were calculated. The predictive efficacy of [¹⁸F]FET PET and CBF in determining MGMT promoter methylation status of glioma were evaluated by whole tumor analysis and stereotactic biopsy. The correlation between PET/MR parameters and MGMT promoter methylation were analyzed using histological specimens acquired from multiple stereotactic biopsies.

Results

Based on the analysis of whole tumor volume and biopsy site, TBRmean, TBRmax, nCBFmean, and nCBFmax showed no statistically significant differences between gliomas with and without MGMT promoter methylation (all p > 0.05). Furthermore, stereotactic biopsy demonstrated that TBRmean, TBRmax, nCBFmean, and nCBFmax showed no correlation with MGMT promoter methylation (r = −0.117, p = 0.579; r = −0.161, p = 0.443; r = −0.271, p = 0.191; r = −0.300, p = 0.145; respectively).

Conclusions

MGMT promoter methylation status shows no effect on [¹⁸F]FET uptake and CBF of ASL in gliomas. Stereotactic biopsy validates it and further reveals there is no correlation of [¹⁸F]FET PET uptake and CBF with the percentages of MGMT promoter methylation.

Key Points

• Based on whole tumor VOI assessment, MGMT promoter methylation status shows no effect on [ ¹⁸ F]FET uptake and CBF of ASL in gliomas.

• For WHO grade IV glioblastomas, [ ¹⁸ F]FET PET and ASL parameters based on hybrid PET/MR fail to predict the MGMT promoter methylation status.

• Stereotactic image–based histology reveals that there is no correlation of [ ¹⁸ F]FET PET uptake and CBF with the status and percentages of MGMT promoter methylation in gliomas.

Nur mit Berechtigung zugänglich

Rogers TW, Toor G, Drummond K et al (2018) The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas. J Neurooncol 137:181–189. https://doi.org/10.1007/s11060-017-2710-7CrossRefPubMed

Oldrini B, Vaquero-Siguero N, Mu Q et al (2020) MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nat Commun 11:3883. https://doi.org/10.1038/s41467-020-17717-0CrossRefPubMedCentralPubMed

Bell EH, Zhang P, Fisher BJ et al (2018) Association of MGMT promoter methylation status with survival outcomes in patients with high-risk glioma treated with radiotherapy and temozolomide: an analysis from the NRG Oncology/RTOG 0424 trial. JAMA Oncol 4:1405–1409. https://doi.org/10.1001/jamaoncol.2018.1977CrossRefPubMed

Ludwig K, Kornblum HI (2017) Molecular markers in glioma. J Neurooncol 134:505–512. https://doi.org/10.1007/s11060-017-2379-yCrossRefPubMedCentralPubMed

Zhou M, Niu C, Jia L, He H (2019) The value of MGMT promote methylation and IDH-1 mutation on diagnosis of pseudoprogression in patients with high-grade glioma: A meta-analysis. Medicine (Baltimore) 98:e18194. https://doi.org/10.1097/MD.0000000000018194CrossRef

Wu H, Deng Z, Wang H et al (2019) MGMT autoantibodies as a potential prediction of recurrence and treatment response biomarker for glioma patients. Cancer Med 8:4359–4369. https://doi.org/10.1002/cam4.2346CrossRefPubMedCentralPubMed

Law I, Albert NL, Arbizu J et al (2018) Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0. Eur J Nucl Med Mol Imaging 46:540–557. https://doi.org/10.1007/s00259-018-4207-9CrossRefPubMedCentralPubMed

Kebir S, Weber M, Lazaridis L et al (2019) Hybrid C-11-MET PET/MRI combined with “machine learning” in glioma diagnosis according to the revised glioma WHO Classification 2016. Clin Nucl Med 44:214–220. https://doi.org/10.1097/RLU.0000000000002398CrossRefPubMed

Cimini A, Chiaravalloti A, Ricci M, Villani V, Vanni G, Schillaci O (2020) MGMT promoter methylation and IDH1 mutations do not affect [18F]FDOPA uptake in primary brain tumors. Int J Mol Sci 21:7598. https://doi.org/10.3390/ijms21207598CrossRefPubMedCentral

10.

Song S, Cheng Y, Ma J, et al (2020) Simultaneous FET-PET and contrast-enhanced MRI based on hybrid PET/MR improves delineation of tumor spatial biodistribution in gliomas: a biopsy validation study. Eur J Nucl Med Mol Imaging 47:1458–1467. https:// doi:https://doi.org/10.1007/s00259-019-04656-2

11.

Okita Y, Nonaka M, Shofuda T et al (2014) (11)C-methinine uptake correlates with MGMT promoter methylation in nonenhancing gliomas. Clin Neurol Neurosurg. 125:212–216. https://doi.org/10.1016/j.clineuro.2014.08.004CrossRefPubMed

12.

Langen KJ, Stoffels G, Filss C et al (2017) Imaging of amino acid transport in brain tumours: positron emission tomography with O-(2-[18F]fluoroethyl)-L-tyrosine (FET). Methods 130:124–134. https://doi.org/10.1016/j.ymeth.2017.05.019CrossRefPubMed

13.

Verger A, Stoffels G, Bauer EK et al (2018) Static and dynamic 18F–FET PET for the characterization of gliomas defined by IDH and 1p/19q status. Eur J Nucl Med Mol Imaging 45:443–451. https://doi.org/10.1007/s00259-017-3846-6CrossRefPubMed

14.

Vettermann F, Suchorska B, Unterrainer M et al (2019) Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic [¹⁸F]FET PET. Eur J Nucl Med Mol Imaging 46:2581–2589. https://doi.org/10.1007/s00259-019-04477-3

15.

Haubold J, Demircioglu A, Gratz M et al (2020) Non-invasive tumor decoding and phenotyping of cerebral gliomas utilizing multiparametric [¹⁸F]FET PET-MRI and MR Fingerprinting. Eur J Nucl Med Mol Imaging 47:1435–1445. https://doi.org/10.1007/s00259-019-04602-2CrossRefPubMed

16.

Song S, Cheng Y, Ma J et al (2020) Simultaneous FET-PET and contrast-enhanced MRI based on hybrid PET/MR improves delineation of tumor spatial biodistribution in gliomas: a biopsy validation study. Eur J Nucl Med Mol Imaging 47:1458–1467. https://doi.org/10.1007/s00259-019-04656-2CrossRefPubMedCentralPubMed

17.

Pang H, Dang X, Ren Y et al (2019) 3D-ASL perfusion correlates with VEGF expression and overall survival in glioma patients: comparison of quantitative perfusion and pathology on accurate spatial location-matched basis. J Magn Reson Imaging 50:209–220. https://doi.org/10.1002/jmri.26562CrossRefPubMed

18.

Sanvito F, Castellano A, Falini A (2021) Advancements in neuroimaging to unravel biological and molecular features of brain tumors. Cancers (Basel) 13:424. https://doi.org/10.3390/cancers13030424CrossRef

19.

Brendle C, Hempel J, Schittenhelm J et al (2018) Glioma grading by dynamic susceptibility contrast perfusion and (11)C-methionine positron emission tomography using different regions of interest. Neuroradiology 60:381–389. https://doi.org/10.1007/s00234-018-1993-5CrossRefPubMed

20.

Yoo R, Yun TJ, Hwang I et al (2020) Arterial spin labeling perfusion-weighted imaging aids in prediction of molecular biomarkers and survival in glioblastomas. Eur Radiol 30:1202–1211. https://doi.org/10.1007/s00330-019-06379-2CrossRefPubMed

21.

Han Y, Yan LF, Wang XB et al (2018) Structural and advanced imaging in predicting MGMT promoter methylation of primary glioblastoma: a region of interest based analysis. BMC Cancer 18:215. https://doi.org/10.1186/s12885-018-4114-2CrossRefPubMedCentralPubMed

22.

Aum DJ, Kim DH, Beaumont TL, Leuthardt EC, Dunn GP, Kim AH (2014) Molecular and cellular heterogeneity: the hallmark of glioblastoma. Neurosurg Focu 37:E11. https://doi.org/10.3171/2014.9.FOCUS14521CrossRef

23.

Parker NR, Hudson AL, Khong P et al (2016) Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma. Sci Rep 6:22477. https://doi.org/10.1038/srep22477CrossRefPubMedCentralPubMed

24.

Munck Af Rosenschold P, Costa J, Engelholm SA et al (2015) Impact of [18F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma. Neuro Oncol 17:757–763. https://doi.org/10.1093/neuonc/nou316CrossRefPubMed

25.

Pauleit D, Floeth F, Hamacher K et al (2005) O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain 128:678–687. https://doi.org/10.1093/brain/awh399CrossRefPubMed

26.

Wang L, Li Z, Liu C et al (2017) Comparative assessment of three methods to analyze MGMT methylation status in a series of 350 gliomas and gangliogliomas. Pathol Res Pract. 213:1489–1493. https://doi.org/10.1016/j.prp.2017.10.007CrossRefPubMed

27.

Hegi ME, Diserens A, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. https://doi.org/10.1056/NEJMoa043331CrossRefPubMed

28.

Wick W, Roth P, Hartmann C et al (2016) Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 18:1529–1537. https://doi.org/10.1093/neuonc/now133CrossRefPubMedCentralPubMed

29.

Eoli M, Menghi F, Bruzzone MG et al (2007) Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival. Clin Cancer Res 13:2606–2613. https://doi.org/10.1158/1078-0432.CCR-06-2184CrossRefPubMed

30.

Kickingereder P, Bonekamp D, Nowosielski M et al (2016) Radiogenomics of glioblastoma: machine learning-based classification of molecular characteristics by using multiparametric and multiregional MR imaging features. Radiology 281:907–918. https://doi.org/10.1148/radiol.2016161382CrossRefPubMed

31.

Lee MK, Park JE, Jo Y, Park SY, Kim SJ, Kim HS (2020) Advanced imaging parameters improve the prediction of diffuse lower-grade gliomas subtype, IDH mutant with no 1p19q codeletion: added value to the T2/FLAIR mismatch sign. Eur Radio 30:844–854. https://doi.org/10.1007/s00330-019-06395-2CrossRef

32.

Filss CP, Galldiks N, Stoffels G et al (2014) Comparison of [¹⁸F]FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med 55:540–545. https://doi.org/10.2967/jnumed.113.129007CrossRefPubMed

33.

Albert NL, Winkelmann I, Suchorska B et al (2016) Early static [¹⁸F]FET-PET scans have a higher accuracy for glioma grading than the standard 20–40 min scans. Eur J Nucl Med Mol Imaging 43:1105–1114. https://doi.org/10.1007/s00259-015-3276-2CrossRefPubMed

34.

Kunz M, Thon N, Eigenbrod S et al (2011) Hot spots in dynamic (FET)-F-18-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro Oncol 13:307–316. https://doi.org/10.1093/neuonc/noq196CrossRefPubMedCentralPubMed

35.

Langen KJ, Watts C (2016) Neuro-oncology: amino acid PET for brain tumours - ready for the clinic? Nat Rev Neurol 12:375–376. https://doi.org/10.1038/nrneurol.2016.80CrossRefPubMed

36.

Vettermann FJ, Felsberg J, Reifenberger G et al (2018) Characterization of diffuse gliomas with histone H3-G34 mutation by MRI and dynamic [¹⁸F]FET PET. Clin Nucl Med 43:895–898. https://doi.org/10.1097/RLU.0000000000002300CrossRefPubMed

37.

Hua T, Zhou W, Zhou Z, Guan Y, Li M (2021) Heterogeneous parameters based on [¹⁸F]FET PET imaging can non-invasively predict tumor grade and isocitrate dehydrogenase gene 1 mutation in untreated gliomas. Quant Imaging Med Surg 11:317–327. https://doi.org/10.21037/qims-20-723CrossRefPubMedCentralPubMed

38.

Lopci E, Riva M, Olivari L et al (2017) Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma. Eur J Nucl Med Mol Imaging 44:1155–1164. https://doi.org/10.1007/s00259-017-3618-3CrossRefPubMed

39.

Okita Y, Shofuda T, Kanematsu D et al (2018) Stereotactic image-based histological analysis reveals a correlation between (11)C-methionine uptake and MGMT promoter methylation in non-enhancing gliomas. Oncol Lett 16:1924–1930. https://doi.org/10.3892/ol.2018.8866CrossRefPubMedCentralPubMed

40.

Glaudemans AW, Enting RH, Heesters MA et al (2013) Value of ¹¹C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging 40:615–635. https://doi.org/10.1007/s00259-012-2295-5CrossRefPubMed

41.

Lisova K, Chen BY, Wang J, Fong KM, Clark PM, van Dam RM (2019) Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET). EJNMMI Radiopharm Chem 5:1. https://doi.org/10.1186/s41181-019-0082-3CrossRefPubMedCentralPubMed

42.

Kubota K (2001) From tumor biology to clinical Pet: a review of positron emission tomography (PET) in oncology. Ann Nucl Med 15:471–486. https://doi.org/10.1007/BF02988499CrossRefPubMed

43.

Yamashita K, Hiwatashi A, Togao O et al (2016) MR imaging-based analysis of glioblastoma multiforme: estimation of IDH1 mutation status. AJNR Am J Neuroradiol 37:58–65. https://doi.org/10.3174/ajnr.A4491CrossRefPubMedCentralPubMed

44.

Wang N, Xie SY, Liu HM, Chen GQ, Zhang WD (2019) Arterial spin labeling for glioma grade discrimination: correlations with IDH1 genotype and 1p/19q status. Transl Oncol 12:749–756. https://doi.org/10.1016/j.tranon.2019.02.013CrossRefPubMedCentralPubMed

45.

Wolf RL, Wang J, Wang S et al (2005) Grading of CNS neoplasms using continuous arterial spin labeled perfusion MR imaging at 3 Tesla. J Magn Reson Imaging 22:475–482. https://doi.org/10.1002/jmri.20415CrossRefPubMed

46.

Parmar C, Rios Velazquez E, Leijenaar R et al (2014) Robust Radiomics feature quantification using semiautomatic volumetric segmentation. PLoS One 9:e102107. https://doi.org/10.1371/journal.pone.0102107CrossRefPubMedCentralPubMed

Titel: MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study
verfasst von: Shuangshuang Song
Yi Shan
Leiming Wang
Ye Cheng
Hongwei Yang
Guoguang Zhao
Zhenguang Wang
Jie Lu
Publikationsdatum: 22.02.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: European Radiology / Ausgabe 8/2022
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-022-08606-9

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

MGMT promoter methylation status shows no effect on [¹⁸F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study