Early static 18F-FET-PET scans have a higher accuracy for glioma grading than the standard 20–40 min scans

  • Nathalie L. AlbertEmail author
  • Isabel Winkelmann
  • Bogdana Suchorska
  • Vera Wenter
  • Christine Schmid-Tannwald
  • Erik Mille
  • Andrei Todica
  • Matthias Brendel
  • Jörg-Christian Tonn
  • Peter Bartenstein
  • Christian la Fougère
Original Article



Current guidelines for glioma imaging by positron emission tomography (PET) using the amino acid analogue O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) recommend image acquisition from 20–40 min post injection (p.i.). The maximal tumour-to-background evaluation (TBRmax) obtained in these summation images does not enable reliable differentiation between low and high grade glioma (LGG and HGG), which, however, can be achieved by dynamic 18F-FET-PET. We investigated the accuracy of tumour grading using TBRmax values at different earlier time points after tracer injection.


Three hundred and fourteen patients with histologically proven primary diagnosis of glioma (131 LGG, 183 HGG) who had undergone 40-min dynamic 18F-FET-PET scans were retrospectively evaluated. TBRmax was assessed in the standard 20–40 min summation images, as well as in summation images from 0–10 min, 5–15 min, 5–20 min, and 15–30 min p.i., and kinetic analysis was performed. TBRmax values and kinetic analysis were correlated with histological classification. ROC analyses were performed for each time frame and sensitivity, specificity, and accuracy were assessed.


TBRmax values in the earlier summation images were significantly better for tumour grading (P < 0.001) when compared to standard 20–40 min scans, with best results for the early 5–15 min scan. This was due to higher TBRmax in the HGG (3.9 vs. 3.3; p < 0.001), while TBRmax remained nearly stable in the LGG (2.2 vs. 2.1). Overall, accuracy increased from 70 % in the 20–40 min analysis to 77 % in the 5–15 min images, but did not reach the accuracy of dynamic analysis (80 %).


Early TBRmax assessment (5–15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20–40 min p.i.) mainly caused by the characteristic high 18F-FET uptake of HGG in the initial phase. Therefore, when dynamic 18F-FET-PET cannot be performed, early TBRmax assessment can be considered as an alternative for tumour grading.


Glioma grading 18F-FET-PET TBRmax 



Parts of this paper originate from the doctoral thesis of Isabel Winkelmann. We thank Dr. Markus Diemling for the technical support.

Compliance with ethical standards

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 was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    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;114:97–109. doi: 10.1007/s00401-007-0243-4.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Jansen NL, Graute V, Armbruster L, Suchorska B, Lutz J, Eigenbrod S, et al. MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET? Eur J Nucl Med Mol Imaging. 2012;39:1021–9. doi: 10.1007/s00259-012-2109-9.CrossRefPubMedGoogle Scholar
  3. 3.
    Scott JN, Brasher PM, Sevick RJ, Rewcastle NB, Forsyth PA. How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology. 2002;59:947–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Kondziolka D, Lunsford LD, Martinez AJ. Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low-grade) astrocytoma. J Neurosurg. 1993;79:533–6. doi: 10.3171/jns.1993.79.4.0533.CrossRefPubMedGoogle Scholar
  5. 5.
    Bisdas S, Ritz R, Bender B, Braun C, Pfannenberg C, Reimold M, et al. Metabolic mapping of gliomas using hybrid MR-PET imaging: feasibility of the method and spatial distribution of metabolic changes. Investig Radiol. 2013;48:295–301. doi: 10.1097/RLI.0b013e31827188d6.CrossRefGoogle Scholar
  6. 6.
    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;128:678–87. doi: 10.1093/brain/awh399.CrossRefPubMedGoogle Scholar
  7. 7.
    la Fougere C, Suchorska B, Bartenstein P, Kreth FW, Tonn JC. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncol. 2011;13:806–19. doi: 10.1093/neuonc/nor054.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pafundi DH, Laack NN, Youland RS, Parney IF, Lowe VJ, Giannini C, et al. Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. Neuro Oncol. 2013;15:1058–67. doi: 10.1093/neuonc/not002.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Vees H, Senthamizhchelvan S, Miralbell R, Weber DC, Ratib O, Zaidi H. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients. Eur J Nucl Med Mol Imaging. 2009;36:182–93. doi: 10.1007/s00259-008-0943-6.CrossRefPubMedGoogle Scholar
  10. 10.
    Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, et al. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res. 2004;10:7163–70. doi: 10.1158/1078-0432.CCR-04-0262.CrossRefPubMedGoogle Scholar
  11. 11.
    Jansen NL, Suchorska B, Schwarz SB, Eigenbrod S, Lutz J, Graute V, et al. [18F]fluoroethyltyrosine-positron emission tomography-based therapy monitoring after stereotactic iodine-125 brachytherapy in patients with recurrent high-grade glioma. Mol Imaging. 2013;12:137–47.PubMedGoogle Scholar
  12. 12.
    Galldiks N, Stoffels G, Filss C, Rapp M, Blau T, Tscherpel 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 Oncol. 2015. doi: 10.1093/neuonc/nov088.Google Scholar
  13. 13.
    Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42:685–95. doi: 10.1007/s00259-014-2959-4.CrossRefPubMedGoogle Scholar
  14. 14.
    Herrmann K, Czernin J, Cloughesy T, Lai A, Pomykala KL, Benz MR, et al. Comparison of visual and semiquantitative analysis of 18F-FDOPA-PET/CT for recurrence detection in glioblastoma patients. Neuro Oncol. 2014;16:603–9. doi: 10.1093/neuonc/not166.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    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;40:615–35. doi: 10.1007/s00259-012-2295-5.CrossRefPubMedGoogle Scholar
  16. 16.
    Popperl G, Kreth FW, Mehrkens JH, Herms J, Seelos K, Koch W, 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;34:1933–42. doi: 10.1007/s00259-007-0534-y.CrossRefPubMedGoogle Scholar
  17. 17.
    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
  18. 18.
    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;33:1374–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Popperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, et al. Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med. 2006;47:393–403.PubMedGoogle Scholar
  20. 20.
    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;55:198–203. doi: 10.2967/jnumed.113.122333.CrossRefPubMedGoogle Scholar
  21. 21.
    Kunz M, Thon N, Eigenbrod S, Hartmann C, Egensperger R, Herms J, et al. Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro Oncol. 2011;13:307–16. doi: 10.1093/neuonc/noq196.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wen PY, Norden AD, Drappatz J, Quant E. Response assessment challenges in clinical trials of gliomas. Current oncology reports. 2010;12:68–75. doi: 10.1007/s11912-009-0078-3.CrossRefPubMedGoogle Scholar
  23. 23.
    Galldiks N, Stoffels G, Ruge MI, Rapp M, Sabel M, Reifenberger G, 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;54:2046–54. doi: 10.2967/jnumed.113.123836.CrossRefPubMedGoogle Scholar
  24. 24.
    Dunkl V, Cleff C, Stoffels G, Judov N, Sarikaya-Seiwert S, Law I, et al. The usefulness of dynamic O-(2-18F-fluoroethyl)-L-tyrosine PET in the clinical evaluation of brain tumors in children and adolescents. J Nucl Med. 2015;56:88–92. doi: 10.2967/jnumed.114.148734.CrossRefPubMedGoogle Scholar
  25. 25.
    Calcagni ML, Galli G, Giordano A, Taralli S, Anile C, Niesen A, et al. Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading: assessment of individual probability of malignancy. Clin Nucl Med. 2011;36:841–7. doi: 10.1097/RLU.0b013e3182291b40.CrossRefPubMedGoogle Scholar
  26. 26.
    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;56:9–15. doi: 10.2967/jnumed.114.144675.CrossRefPubMedGoogle Scholar
  27. 27.
    Derlon JM, Chapon F, Noel MH, Khouri S, Benali K, Petit-Taboue MC, et al. Non-invasive grading of oligodendrogliomas: correlation between in vivo metabolic pattern and histopathology. Eur J Nucl Med. 2000;27:778–87.CrossRefPubMedGoogle Scholar
  28. 28.
    Kracht LW, Friese M, Herholz K, Schroeder R, Bauer B, Jacobs A, et al. Methyl-[11C]- l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma. Eur J Nucl Med Mol Imaging. 2003;30:868–73. doi: 10.1007/s00259-003-1148-7.CrossRefPubMedGoogle Scholar
  29. 29.
    Bisdas S, Kirkpatrick M, Giglio P, Welsh C, Spampinato MV, Rumboldt Z. Cerebral blood volume measurements by perfusion-weighted MR imaging in gliomas: ready for prime time in predicting short-term outcome and recurrent disease? AJNR Am J Neurorad. 2009;30:681–8. doi: 10.3174/ajnr.A1465.CrossRefGoogle Scholar
  30. 30.
    Jansen NL, Schwartz C, Graute V, Eigenbrod S, Lutz J, Egensperger R, 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 Oncol. 2012;14:1473–80. doi: 10.1093/neuonc/nos259.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lohmann P, Herzog H, Rota Kops E, Stoffels G, Judov N, Filss C, et al. Dual-time-point O-(2-[F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas. Eur Radiol. 2015. doi: 10.1007/s00330-015-3691-6.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nathalie L. Albert
    • 1
    Email author
  • Isabel Winkelmann
    • 1
  • Bogdana Suchorska
    • 2
  • Vera Wenter
    • 1
  • Christine Schmid-Tannwald
    • 3
  • Erik Mille
    • 1
  • Andrei Todica
    • 1
  • Matthias Brendel
    • 1
  • Jörg-Christian Tonn
    • 2
  • Peter Bartenstein
    • 1
  • Christian la Fougère
    • 4
  1. 1.Department of Nuclear MedicineLudwig-Maximilians-University MunichMunichGermany
  2. 2.Department of NeurosurgeryLudwig-Maximilians-University MunichMunichGermany
  3. 3.Institute for Clinical RadiologyLudwig-Maximilians-University MunichMunichGermany
  4. 4.Division of Nuclear Medicine and Clinical Molecular Imaging, Department of RadiologyUniversity of TübingenTübingenGermany

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