Biological tumour volumes of gliomas in early and standard 20–40 min 18F-FET PET images differ according to IDH mutation status

  • M. Unterrainer
  • I. Winkelmann
  • B. Suchorska
  • A. Giese
  • V. Wenter
  • F. W. Kreth
  • J. Herms
  • P. Bartenstein
  • J. C. Tonn
  • N. L. Albert
Original Article



For the clinical evaluation of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET images, the use of standard summation images obtained 20–40 min after injection is recommended. However, early summation images obtained 5–15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification.


The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5–15 min and standard 20–40 min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status).


In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53).


BTVs delineated in early and standard summation images differed significantly in more than half of gliomas. While the standard summation images seem appropriate for delineation of LGG as well as IDH-mutant gliomas, a remarkably high percentage of HGG and, particularly, IDH-wildtype gliomas were depicted with significantly larger volumes in early summation images. This finding might be of interest for optimization of treatment planning (e.g. radiotherapy) in accordance with the individual IDH mutation status.


Glioma FET PET BTV IDH 1p/19q codeletion 



Parts of this paper originate from the doctoral thesis of Isabel Winkelmann.

Compliance with ethical standards

Conflicts of interest


Ethical approval

Ethical approval of the retrospective study protocol was given by the institutional review board of the LMU (no. 606–16) in accordance with the ICH Guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki.

Informed consent

All patients gave written informed consent prior to the PET examination.


  1. 1.
    Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, 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 Oncol. 2016;18(9):1199–208.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Galldiks N, Rapp M, Stoffels G, Fink GR, Shah NJ, Coenen HH, 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
  3. 3.
    Jansen NL, Suchorska B, Wenter V, Eigenbrod S, Schmid-Tannwald C, Zwergal A, et al. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients. J Nucl Med. 2014;55(2):198–203.CrossRefPubMedGoogle Scholar
  4. 4.
    Jansen NL, Suchorska B, Wenter V, Schmid-Tannwald C, Todica A, Eigenbrod S, 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
  5. 5.
    Unterrainer M, Schweisthal F, Suchorska B, Wenter V, Schmid-Tannwald C, Fendler WP, et al. Serial 18F-FET PET imaging of primarily 18F-FET-negative gGlioma: does it make sense? J Nucl Med. 2016;57(8):1177–82.Google Scholar
  6. 6.
    Pirotte BJ, Levivier M, Goldman S, Massager N, Wikler D, Dewitte O, et al. Positron emission tomography-guided volumetric resection of supratentorial high-grade gliomas: a survival analysis in 66 consecutive patients. Neurosurgery. 2009;64(3):471–81.CrossRefPubMedGoogle Scholar
  7. 7.
    Niyazi M, Geisler J, Siefert A, Schwarz SB, Ganswindt U, Garny S, et al. FET-PET for malignant glioma treatment planning. Radiother Oncol. 2011;99(1):44–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Piroth MD, Pinkawa M, Holy R, Stoffels G, Demirel C, Attieh C, et al. Integrated-boost IMRT or 3-D-CRT using FET-PET based auto-contoured target volume delineation for glioblastoma multiforme – a dosimetric comparison. Radiat Oncol. 2009;4:57.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Langen KJ, Bartenstein P, Boecker H, Brust P, Coenen HH, Drzezga A, et al. German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids. Nuklearmedizin. 2011;50:167–73.CrossRefPubMedGoogle Scholar
  10. 10.
    Vander Borght T, Asenbaum S, Bartenstein P, Halldin C, Kapucu Ö, Van Laere K, et al. EANM procedure guidelines for brain tumour imaging using labelled amino acid analogues. Eur J Nucl Med Mol Imaging. 2006;33(11):1374–80.CrossRefPubMedGoogle Scholar
  11. 11.
    Albert NL, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E, 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
  12. 12.
    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.CrossRefPubMedGoogle Scholar
  13. 13.
    Weller M, Pfister SM, Wick W, Hegi ME, Reifenberger G, Stupp R. Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol. 2013;14(9):e370–e9.CrossRefPubMedGoogle Scholar
  14. 14.
    Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129(4):585–96.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B, et al. Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas. Neuro-Oncology. 2016;18(8):1099–108.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Unterrainer M, Vettermann F, Brendel M, Holzgreve A, Lifschitz M, Zähringer M, et al. Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment? EJNMMI Res. 2017;7(1):48.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Muller HW, 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
  18. 18.
    Wyss M, Hofer S, Bruehlmeier M, Hefti M, Uhlmann C, Bärtschi E, et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol. 2009;95(1):87–93.CrossRefPubMedGoogle Scholar
  19. 19.
    Galldiks N, Langen K-J, Holy R, Pinkawa M, Stoffels G, Nolte KW, 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;53(7):1048–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97–109.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Thon N, Eigenbrod S, Kreth S, Lutz J, Tonn JC, Kretzschmar H, et al. IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival. Cancer. 2012;118(2):452–60.CrossRefPubMedGoogle Scholar
  22. 22.
    Thon N, Eigenbrod S, Grasbon-Frodl EM, Ruiter M, Mehrkens JH, Kreth S, et al. Novel molecular stereotactic biopsy procedures reveal intratumoral homogeneity of loss of heterozygosity of 1p/19q and TP53 mutations in World Health Organization grade II gliomas. J Neuropathol Exp Neurol. 2009;68(11):1219–28.CrossRefPubMedGoogle Scholar
  23. 23.
    Suchorska B, Giese A, Biczok A, Unterrainer M, Weller M, Drexler M, et al. Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma. Neuro Oncol. 2018;20(2):279–88.CrossRefPubMedGoogle Scholar
  24. 24.
    Lohmann P, Herzog H, Rota Kops E, Stoffels G, Judov N, Filss C, et al. Dual-time-point O-(2-[18F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas. Eur Radiol. 2015;25(10):3017–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM. Selective expression of the large neutral amino acid transporter at the blood–brain barrier. Proc Natl Acad Sci U S A. 1999;96(21):12079–84.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Habermeier A, Graf J, Sandhöfer B, Boissel J-P, Roesch F, Closs EI. System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. 2015;47(2):335–44.CrossRefPubMedGoogle Scholar
  27. 27.
    Harat M, Małkowski B, Makarewicz R. Pre-irradiation tumour volumes defined by MRI and dual time-point FET-PET for the prediction of glioblastoma multiforme recurrence: a prospective study. Radiother Oncol. 2016;120(2):241–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Moller S, Law I, Af Rosenschold PM, Costa J, Poulsen HS, Engelholm SA, et al. Prognostic value of 18F-FET PET imaging in re-irradiation of high-grade glioma: results of a phase I clinical trial. Radiother Oncol. 2016;121(1):132–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Suchorska B, Jansen NL, Linn J, Kretzschmar H, Janssen H, Eigenbrod S, et al. Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology. 2015;84(7):710–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Roelcke U, Wyss MT, Nowosielski M, Rudà R, Roth P, Hofer S, et al. Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas. Neuro Oncol. 2016;18(5):744–51.CrossRefPubMedGoogle Scholar
  31. 31.
    Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H, et al. O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med. 2011;52(6):856–64.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication March/2018

Authors and Affiliations

  • M. Unterrainer
    • 1
  • I. Winkelmann
    • 1
  • B. Suchorska
    • 2
  • A. Giese
    • 3
  • V. Wenter
    • 1
  • F. W. Kreth
    • 2
  • J. Herms
    • 3
  • P. Bartenstein
    • 1
    • 4
  • J. C. Tonn
    • 2
    • 4
  • N. L. Albert
    • 1
    • 4
  1. 1.Department of Nuclear MedicineUniversity Hospital, LMU MunichMunichGermany
  2. 2.Department of NeurosurgeryUniversity Hospital, LMU MunichMunichGermany
  3. 3.Department of NeuropathologyUniversity Hospital, LMU MunichMunichGermany
  4. 4.German Cancer Consortium (DKTK), Partner Site Munich; and German Cancer Research Center (DKFZ)HeidelbergGermany

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