Re-evaluation of the diagnostic performance of 11C-methionine PET/CT according to the 2016 WHO classification of cerebral gliomas

  • Dongwoo Kim
  • Joong-Hyun Chun
  • Se Hoon Kim
  • Ju Hyung Moon
  • Seok-Gu Kang
  • Jong Hee Chang
  • Mijin YunEmail author
Original Article



We evaluated the usefulness of 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) for grading cerebral gliomas according to the 2016 WHO classification with special emphasis on the presence of the isocitrate dehydrogenase 1 (IDH1) gene mutation and 1p/19q codeletion.


In total, 144 patients underwent MET PET/CT before surgery. The ratios of the maximum standardized uptake value (SUV) of the gliomas to the mean SUV of the contralateral cortex on MET PET/CT (MET TNR) were calculated.


The median MET TNRs in IDH1-mutant and IDH1-wildtype tumours were 1.95 and 3.35, respectively. From among 74 IDH1-mutant tumours, the oligodendrogliomas showed a higher median MET TNR than the astrocytic tumours (2.90 vs. 1.40, P < 0.001). In grade II, III and IV IDH1-mutant astrocytic tumours, the median MET TNRs were 1.20, 2.05 and 2.20, respectively (grade II vs. grade III, P < 0.0001; grade II vs. grade IV, P = 0.023). In oligodendrogliomas, the MET TNR was lower fin grade II tumours than in grade III tumours (2.30 vs. 3.30 P = 0.008). In differentiating low-grade (grade II) from high-grade (grade III and IV) gliomas, receiver operating characteristic analysis showed a higher area under the curve for wildtype tumours (0.976) than for all tumours (0.852; P < 0.001) and IDH1-mutant tumours (0.817; P = 0.004).


IDH1-mutant tumours showed lower MET uptake than IDH1-wildtype tumours. Regardless of IDH1 mutation status, oligodendrogliomas with 1p/19q codeletion showed MET uptake as high as that in high-grade IDH1-wildtype tumours. Therefore, MET uptake for glioma grading was more consistent for IDH1-wildtype tumours than for IDH1-mutant tumours.


Glioma 11C-Methionine PET/CT IDH1 mutation Grading 



Dongwoo Kim, Joong-Hyun Chun and Mijin Yun had primary responsibility for study design, statistical analysis, coordinating the study, writing the manuscript and revision of the manuscript. Dongwoo Kim, Se Hoon Kim, Ju Hyung Moon, Seok-Gu Kang, Jong Hee Chang and Mijin Yun contributed to data acquisition, analysis and interpretation.


This work was supported partially by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (NRF-2012R1A1A3008042, NRF-2016R1E1A1A01943303, and NRF-2018M3C7A1056898).

Compliance with ethical standards

Conflicts of interest


Ethical approval

All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Formal consent is not required for this type of study.

Informed consent

The Institutional Review Board of our university approved this retrospective study, and the requirement to obtain informed consent was waived.

Supplementary material

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Supplementary Fig. 1

ROC curve for IDH1-wildtype gliomas versus IDH1-mutant gliomas. (PNG 80 kb)

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High resolution image (TIF 27678 kb)
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Supplementary Fig. 2

The tumour SUVmax to contralateral cortex SUVmean 11C-MET ratios (MET TNR) differed significantly between WHO grades in IDH1-mutant tumours. In IDH1-mutant tumours, MET TNR was higher in oligodendrogliomas with the 1p/19q codeletion than in astrocytic tumours without the codeletion (circles outliers, > 1.5 times interquartile range; asterisks extreme outliers, >3 times interquartile range). (PNG 395 kb)

259_2019_4337_MOESM2_ESM.tif (4.4 mb)
High resolution image (TIF 4485 kb)
259_2019_4337_Fig6_ESM.png (253 kb)
Supplementary Fig. 3

The tumour SUVmax to contralateral cortex SUVmean 11C-MET ratios (MET TNR) of grade II oligodendrogliomas were compared with those of other gliomas according to the new 2016 WHO tumour classification (circles outliers, > 1.5 times interquartile range; asterisks extreme outliers, >3 times interquartile range). (PNG 253 kb)

259_2019_4337_MOESM3_ESM.tif (2.6 mb)
High resolution image (TIF 2685 kb)
259_2019_4337_Fig7_ESM.png (267 kb)
Supplementary Fig. 4

The tumour SUVmax to contralateral cortex SUVmean 11C-MET ratios (MET TNR) of grade III oligodendrogliomas were compared with those of other gliomas according to the new 2016 WHO tumour classification (circles outliers, > 1.5 times interquartile range; asterisks extreme outliers, >3 times interquartile range). (PNG 267 kb)

259_2019_4337_MOESM4_ESM.tif (2.8 mb)
High resolution image (TIF 2837 kb)
259_2019_4337_Fig8_ESM.png (81 kb)
Supplementary Fig. 5

ROC curves differentiating low-grade from high-grade gliomas including (a) both IDH1-wildtype and IDH1-mutant tumours, (b) only IDH1-wildtype tumours, and (c) only IDH1-mutant tumours. (PNG 81.2 kb)

259_2019_4337_MOESM5_ESM.tif (14.9 mb)
High resolution image (TIF 15267 kb)


  1. 1.
    Glaudemans AW, Enting RH, Heesters MA, Dierckx RA, van Rheenen RW, Walenkamp AM, et al. Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging. 2013;40(4):615–35. Scholar
  2. 2.
    Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42(3):432–45.Google Scholar
  3. 3.
    Stern PH, Wallace CD, Hoffman RM. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J Cell Physiol. 1984;119(1):29–34. Scholar
  4. 4.
    Narayanan TK, Said S, Mukherjee J, Christian B, Satter M, Dunigan K, et al. A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma. Mol Imaging Biol. 2002;4(2):147–56.CrossRefGoogle Scholar
  5. 5.
    Fuchs BC, Bode BP. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol. 2005;15(4):254–66. Scholar
  6. 6.
    Ishiwata K, Kubota K, Murakami M, Kubota R, Senda M. A comparative study on protein incorporation of L-[methyl-3H]methionine, L-[1-14C]leucine and L-2-[18F]fluorotyrosine in tumor bearing mice. Nucl Med Biol. 1993;20(8):895–9.CrossRefGoogle Scholar
  7. 7.
    Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, et al. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology. 1998;50(5):1316–22.CrossRefGoogle Scholar
  8. 8.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20. Scholar
  9. 9.
    Akagi Y, Yoshimoto K, Hata N, Kuga D, Hatae R, Amemiya T, et al. Reclassification of 400 consecutive glioma cases based on the revised 2016 WHO classification. Brain Tumor Pathol. 2018;35(2):81–9. Scholar
  10. 10.
    Verger A, Stoffels G, Bauer EK, Lohmann P, Blau T, Fink GR, et al. Static and dynamic (18)F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status. Eur J Nucl Med Mol Imaging. 2018;45(3):443–51. Scholar
  11. 11.
    Poetsch N, Woehrer A, Gesperger J, Furtner J, Haug AR, Wilhelm D, et al. Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naive gliomas. Neuro Oncol. 2018;20(3):411–9. Scholar
  12. 12.
    Verger A, Taieb D, Guedj E. Is the information provided by amino acid PET radiopharmaceuticals clinically equivalent in gliomas? Eur J Nucl Med Mol Imaging. 2017;44(8):1408–10. Scholar
  13. 13.
    Lopci E, Riva M, Olivari L, Raneri F, Soffietti R, Piccardo A, et al. Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma. Eur J Nucl Med Mol Imaging. 2017;44(7):1155–64. Scholar
  14. 14.
    Bette S, Gempt J, Delbridge C, Kirschke JS, Schlegel J, Foerster S, et al. Prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine-positron emission tomography imaging for histopathologic characteristics and progression-free survival in patients with low-grade glioma. World Neurosurg. 2016;89:230–9. Scholar
  15. 15.
    Kim D, Kim S, Kim SH, Chang JH, Yun M. Prediction of overall survival based on Isocitrate dehydrogenase 1 mutation and 18F-FDG uptake on PET/CT in patients with cerebral gliomas. Clin Nucl Med. 2018;43(5):311–6. Scholar
  16. 16.
    Verger A, Metellus P, Sala Q, Colin C, Bialecki E, Taieb D, et al. IDH mutation is paradoxically associated with higher (18)F-FDOPA PET uptake in diffuse grade II and grade III gliomas. Eur J Nucl Med Mol Imaging. 2017;44(8):1306–11. Scholar
  17. 17.
    Kato T, Shinoda J, Nakayama N, Miwa K, Okumura A, Yano H, et al. Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography. AJNR Am J Neuroradiol. 2008;29(6):1176–82. Scholar
  18. 18.
    Manabe O, Hattori N, Yamaguchi S, Hirata K, Kobayashi K, Terasaka S, et al. Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging. Eur J Nucl Med Mol Imaging. 2015;42(6):896–904. Scholar
  19. 19.
    Singhal T, Narayanan TK, Jacobs MP, Bal C, Mantil JC. 11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI. J Nucl Med. 2012;53(11):1709–15. Scholar
  20. 20.
    Okubo S, Zhen HN, Kawai N, Nishiyama Y, Haba R, Tamiya T. Correlation of L-methyl-11C-methionine (MET) uptake with L-type amino acid transporter 1 in human gliomas. J Neurooncol. 2010;99(2):217–25. Scholar
  21. 21.
    Kickingereder P, Sahm F, Radbruch A, Wick W, Heiland S, Deimling A, et al. IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma. Sci Rep. 2015;5:16238. Scholar
  22. 22.
    Saito T, Maruyama T, Muragaki Y, Tanaka M, Nitta M, Shinoda J, et al. 11C-methionine uptake correlates with combined 1p and 19q loss of heterozygosity in oligodendroglial tumors. AJNR Am J Neuroradiol. 2013;34(1):85–91. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Dongwoo Kim
    • 1
  • Joong-Hyun Chun
    • 2
  • Se Hoon Kim
    • 3
  • Ju Hyung Moon
    • 4
  • Seok-Gu Kang
    • 4
  • Jong Hee Chang
    • 4
  • Mijin Yun
    • 1
    Email author
  1. 1.Department of Nuclear Medicine, Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of Nuclear MedicineYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of Pathology, Severance HospitalYonsei University College of MedicineSeoulSouth Korea
  4. 4.Department of Neurosurgery, Severance HospitalYonsei University College of MedicineSeoulSouth Korea

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