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Static and dynamic 18F–FET PET for the characterization of gliomas defined by IDH and 1p/19q status

  • Antoine Verger
  • Gabriele Stoffels
  • Elena K. Bauer
  • Philipp Lohmann
  • Tobias Blau
  • Gereon R. Fink
  • Bernd Neumaier
  • Nadim J. Shah
  • Karl-Josef Langen
  • Norbert Galldiks
Original Article

Abstract

Purpose

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2-18F-fluoroethyl)-L-tyrosine (18F–FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion.

Methods

Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18F–FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBRmean/max), as well as dynamic parameters (time-to-peak and slope) of 18F–FET uptake were calculated.

Results

Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBRmean, TBRmax, TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBRmean showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBRmean, TBRmax, TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBRmax or slope (accuracy, 73%).

Conclusion

Data suggest that static and dynamic 18F–FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18F–FET PET.

Keywords

FET pet Glioma IDH mutation 1p/19q co-deletion 

Notes

Funding

This work was supported by the Wilhelm-Sander Stiftung, Germany.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed written consent was obtained from all individual participants included in the study.

References

  1. 1.
    Albert NL, Weller M, Suchorska B, et al. Response assessment in Neuro-oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro-Oncology. 2016;18(9):1199–208.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Albert NL, Winkelmann I, Suchorska B, et al. Early static (18)F-FET-PET scans have a higher accuracy for glioma grading than the standard 20-40 min scans. Eur J Nucl Med Mol Imaging. 2016;43(6):1105–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Jansen NL, Suchorska B, Wenter V, et al. Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma. J Nucl Med. 2015;56(1):9–15.CrossRefPubMedGoogle Scholar
  4. 4.
    Rapp M, Heinzel A, Galldiks N, et al. Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med. 2013;54(2):229–35.CrossRefPubMedGoogle Scholar
  5. 5.
    Piroth MD, Holy R, Pinkawa M, et al. Prognostic impact of postoperative, pre-irradiation (18)F-fluoroethyl-l-tyrosine uptake in glioblastoma patients treated with radiochemotherapy. Radiother Oncol. 2011;99(2):218–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Pauleit D, Floeth F, Hamacher K, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128(Pt 3):678–87.CrossRefPubMedGoogle Scholar
  7. 7.
    Galldiks N, Langen K-J, Holy R, et al. Assessment of treatment response in patients with glioblastoma using O-(2-18F-fluoroethyl)-L-tyrosine PET in comparison to MRI. J Nucl Med. 2012 Jul;53(7):1048–57.CrossRefPubMedGoogle Scholar
  8. 8.
    Suchorska B, Jansen NL, Linn J, et al. Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology. 2015;84(7):710–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Wyss M, Hofer S, Bruehlmeier M, et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neuro-Oncol. 2009;95(1):87–93.CrossRefGoogle Scholar
  10. 10.
    Galldiks N, Rapp M, Stoffels G, et al. Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging. 2013;40(1):22–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Galldiks N, Law I, Pope WB, Arbizu J, Langen K-J. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy. NeuroImage Clin. 2017;13:386–94.CrossRefPubMedGoogle Scholar
  12. 12.
    Jansen NL, Graute V, Armbruster L, et al. MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET? Eur J Nucl Med Mol Imaging. 2012;39(6):1021–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol (Berl). 2007;114(2):97–109.CrossRefGoogle Scholar
  14. 14.
    Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499–508.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol (Berl). 2016;131(6):803–20.CrossRefGoogle Scholar
  16. 16.
    Lopci E, Riva M, Olivari L, 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.CrossRefPubMedGoogle Scholar
  17. 17.
    Verger A, Metellus P, Sala Q, et al. IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas. Eur J Nucl Med Mol Imaging. 2017;44(8):1306–11.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    Bette S, Gempt J, Delbridge C, 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Langen K-J, Bartenstein P, Boecker H, et al. German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids. Nukl Nucl Med. 2011;50(4):167–73.CrossRefGoogle Scholar
  21. 21.
    Herzog H, Langen K-J, Weirich C, et al. High resolution BrainPET combined with simultaneous MRI. Nukl Nucl Med. 2011;50(2):74–82.CrossRefGoogle Scholar
  22. 22.
    Galldiks N, Stoffels G, Filss C, et al. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro-Oncology. 2015;17(9):1293–300.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Ceccon G, Lohmann P, Stoffels G, et al. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro-Oncology. 2017;19(2):281–8.PubMedGoogle Scholar
  24. 24.
    Pöpperl G, Kreth FW, Mehrkens JH, et al. FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. Eur J Nucl Med Mol Imaging. 2007;34(12):1933–42.CrossRefPubMedGoogle Scholar
  25. 25.
    Kunz M, Thon N, Eigenbrod S, et al. Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro-Oncology. 2011;13(3):307–16.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lohmann P, Herzog H, Rota Kops E, et al. Dual-time-point O-(2-[(18)F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas. Eur Radiol. 2015;25(10):3017–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Floeth FW, Pauleit D, Sabel M, et al. Prognostic value of O-(2-18F-fluoroethyl)-L-tyrosine PET and MRI in low-grade glioma. J Nucl Med. 2007;48(4):519–27.CrossRefPubMedGoogle Scholar
  28. 28.
    Galldiks N, Stoffels G, Ruge MI, et al. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET as a diagnostic tool for detection of malignant progression in patients with low-grade glioma. J Nucl Med. 2013;54(12):2046–54.CrossRefPubMedGoogle Scholar
  29. 29.
    Thon N, Kunz M, Lemke L, et al. Dynamic 18 F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses: dynamic PET in suspected low-grade gliomas. Int J Cancer. 2015;136(9):2132–45.CrossRefPubMedGoogle Scholar
  30. 30.
    Jansen NL, Schwartz C, Graute V, et al. Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [(18)F]FET-PET imaging in intracranial WHO grade II and III gliomas. Neuro-Oncology. 2012;14(12):1473–80.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Manabe O, Hattori N, Yamaguchi 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.CrossRefPubMedGoogle Scholar
  32. 32.
    van den Bent MJ, Brandes AA, Taphoorn MJB, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–50.CrossRefPubMedGoogle Scholar
  33. 33.
    Cairncross JG, Wang M, Jenkins RB, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol. 2014;32(8):783–90.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Reuss DE, Mamatjan Y, Schrimpf D, et al. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol (Berl). 2015;129(6):867–73.CrossRefGoogle Scholar
  35. 35.
    Olar A, Wani KM, Alfaro-Munoz KD, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol (Berl). 2015;129(4):585–96.CrossRefGoogle Scholar
  36. 36.
    de la Fuente MI, Young RJ, Rubel J, et al. Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro-Oncology. 2016;18(2):283–90.CrossRefPubMedGoogle Scholar
  37. 37.
    Jiang H, Cui Y, Wang J, Lin S. Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system. Oncotarget. 2017;8(12):20354–61.PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Antoine Verger
    • 1
    • 2
    • 3
    • 4
  • Gabriele Stoffels
    • 1
  • Elena K. Bauer
    • 5
  • Philipp Lohmann
    • 1
  • Tobias Blau
    • 6
  • Gereon R. Fink
    • 1
    • 5
  • Bernd Neumaier
    • 1
  • Nadim J. Shah
    • 1
    • 7
    • 8
  • Karl-Josef Langen
    • 1
    • 8
    • 9
  • Norbert Galldiks
    • 1
    • 5
    • 10
  1. 1.Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5)Forschungszentrum JülichJülichGermany
  2. 2.Department of Nuclear Medicine & Nancyclotep Imaging Platform, CHRU NancyLorraine UniversityNancyFrance
  3. 3.IADI, INSERM, UMR 947Lorraine UniversityNancyFrance
  4. 4.Service de Médecine NucléaireVandoeuvre-les-NancyFrance
  5. 5.Department of NeurologyUniversity Hospital CologneCologneGermany
  6. 6.Department of NeuropathologyUniversity Hospital CologneCologneGermany
  7. 7.Department of NeurologyRWTH Aachen University HospitalAachenGermany
  8. 8.Section JARA-Brain, Juelich-Aachen Research Alliance (JARA)JuelichGermany
  9. 9.Department of Nuclear MedicineRWTH Aachen University HospitalAachenGermany
  10. 10.Center of Integrated Oncology (CIO)Universities of Cologne and BonnCologneGermany

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