Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-l-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake

  • Carina Stegmayr
  • Gabriele Stoffels
  • Elena Rota Kops
  • Philipp Lohmann
  • Norbert Galldiks
  • Nadim J. Shah
  • Bernd Neumaier
  • Karl-Josef Langen
Research Article



O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [18F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR).


[18F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [18F]FET uptake in the normal brain (SUVbrain) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy.


SUVbrain of [18F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUVbrain 1.33 ± 0.1 versus 1.06 ± 0.16 in male and 1.45 ± 0.25 versus 1.31 ± 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUVbrain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBRmax and TBRmean, which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBRmax and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUVbrain.


Dexamethasone treatment appears to increase the [18F]FET uptake in the normal brain. An effect on TBRmax, TBRmean, and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [18F]FET PET.

Key words

PET Brain tumors Amino acids [18F]Fluoroethyltyrosine FET Dexamethasone Tumor-to-brain ratio 



The authors wish to thank Erika Wabbals, Silke Grafmüller, and Sascha Rehbein for technical assistance in radiosynthesis of [18F]FET and Silke Frensch, Suzanne Schaden, and Kornelia Frey for technical assistance in performing the PET measurements.

Compliance with Ethical Standards

The ethics committee of the University of Aachen approved the retrospective data evaluation. There was no conflict with the Declaration of Helsinki. All subjects gave prior written informed consent for the PET investigation and the use of the data for scientific evaluations.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2018_1221_MOESM1_ESM.pdf (286 kb)
ESM 1 (PDF 285 kb)


  1. 1.
    Langen KJ, Watts C (2016) Neuro-oncology: amino acid PET for brain tumours—ready for the clinic? Nat Rev Neurol 12:375–376CrossRefPubMedGoogle Scholar
  2. 2.
    Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, la Fougère C, Pope W, Law I, Arbizu J, Chamberlain MC, Vogelbaum M, Ellingson BM, Tonn JC (2016) 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 18:1199–1208CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Galldiks N, Langen K, Holy R et al (2012) Assessment of treatment response in patients with glioblastoma using [18F]fluoroethyl-L-tyrosine PET in comparison to MRI. J Nucl Med 53:1048–1057CrossRefPubMedGoogle Scholar
  4. 4.
    Pauleit D, Stoffels G, Bachofner A, Floeth FW, Sabel M, Herzog H, Tellmann L, Jansen P, Reifenberger G, Hamacher K, Coenen HH, Langen KJ (2009) Comparison of 18F-FET and 18F-FDG PET in brain tumors. Nucl Med Biol 36:779–787CrossRefPubMedGoogle Scholar
  5. 5.
    Pichler R, Dunzinger A, Wurm G, Pichler J, Weis S, Nußbaumer K, Topakian R, Aigner RM (2010) Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance? Eur J Nucl Med Mol Imaging 37:1521–1528CrossRefPubMedGoogle Scholar
  6. 6.
    Popperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K (2004) Value of O-(2-[18F]fluoroethyl)-L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging 31:1464–1470CrossRefPubMedGoogle Scholar
  7. 7.
    Floeth FW, Pauleit D, Sabel M, Stoffels G, Reifenberger G, Riemenschneider MJ, Jansen P, Coenen HH, Steiger HJ, Langen KJ (2007) Prognostic value of O-(2-18F-fluoroethyl)-L-tyrosine PET and MRI in low-grade glioma. J Nucl Med 48:519–527CrossRefPubMedGoogle Scholar
  8. 8.
    Jansen NL, Suchorska B, Wenter V, Schmid-Tannwald C, Todica A, Eigenbrod S, Niyazi M, Tonn JC, Bartenstein P, Kreth FW, la Fougere C (2015) Prognostic significance of dynamic 18F-FET PET in newly diagnosed astrocytic high-grade glioma. J Nucl Med 56:9–15CrossRefPubMedGoogle Scholar
  9. 9.
    Weckesser M, Langen KJ, Rickert CH, Kloska S, Straeter R, Hamacher K, Kurlemann G, Wassmann H, Coenen HH, Schober O (2005) O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging 32:422–429CrossRefPubMedGoogle Scholar
  10. 10.
    Calcagni ML, Galli G, Giordano A, Taralli S, Anile C, Niesen A, Baum RP (2011) Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading: assessment of individual probability of malignancy. Clin Nucl Med 36:841–847CrossRefPubMedGoogle Scholar
  11. 11.
    Galldiks N, Langen KJ (2015) Applications of PET imaging of neurological tumors with radiolabeled amino acids. Q J Nucl Med Mol Imaging 59:70–82PubMedGoogle Scholar
  12. 12.
    Herholz K, Langen KJ, Schiepers C, Mountz JM (2012) Brain tumors. Semin Nucl Med 42:356–370CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Langen KJ, Hamacher K, Weckesser M, Floeth F, Stoffels G, Bauer D, Coenen HH, Pauleit D (2006) O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol 33:287–294CrossRefPubMedGoogle Scholar
  14. 14.
    Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, Stöcklin G (1999) Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med 40:205–212PubMedGoogle Scholar
  15. 15.
    Kotsarini C, Griffiths PD, Wilkinson ID, Hoggard N (2010) A systematic review of the literature on the effects of dexamethasone on the brain from in vivo human-based studies: implications for physiological brain imaging of patients with intracranial tumors. Neurosurgery 67:1799–1815 discussion 1815CrossRefPubMedGoogle Scholar
  16. 16.
    Sarin R, Murthy V (2003) Medical decompressive therapy for primary and metastatic intracranial tumours. Lancet Neurol 2:357–365CrossRefPubMedGoogle Scholar
  17. 17.
    Stegmayr C, Bandelow U, Oliveira D, Lohmann P, Willuweit A, Filss C, Galldiks N, Lübke JHR, Shah NJ, Ermert J, Langen KJ (2017) Influence of blood-brain barrier permeability on O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas. Eur J Nucl Med Mol Imaging 44:408–416CrossRefPubMedGoogle Scholar
  18. 18.
    Stegmayr C, Oliveira D, Niemietz N, Willuweit A, Lohmann P, Galldiks N, Shah NJ, Ermert J, Langen KJ (2017) Influence of bevacizumab on blood-brain barrier permeability and O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas. J Nucl Med 58:700–705CrossRefPubMedGoogle Scholar
  19. 19.
    Stegmayr C, Schoneck M, Oliveira D et al (2016) Reproducibility of O-(2-18F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas. Eur J Nucl Med Mol Imaging 43:1115–1123CrossRefPubMedGoogle Scholar
  20. 20.
    Hamacher K, Coenen HH (2002) Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot 57:853–856CrossRefPubMedGoogle Scholar
  21. 21.
    Langen KJ, Bartenstein P, Boecker H et al (2011) German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids. Nuklearmedizin 50:167–173CrossRefPubMedGoogle Scholar
  22. 22.
    Herzog H, Langen KJ, Weirich C et al (2011) High resolution BrainPET combined with simultaneous MRI. Nuklearmedizin Nucl Med 50:74–82CrossRefGoogle Scholar
  23. 23.
    Rota Kops E, Hautzel H, Herzog H, Antoch G, Shah NJ (2015) Comparison of template-based versus CT-based attenuation correction for hybrid MR/PET scanners. IEEE Trans Nucl Sci 62:2115–2121CrossRefGoogle Scholar
  24. 24.
    Rapp M, Heinzel A, Galldiks N, Stoffels G, Felsberg J, Ewelt C, Sabel M, Steiger HJ, Reifenberger G, Beez T, Coenen HH, Floeth FW, Langen KJ (2013) Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med 54:229–235CrossRefPubMedGoogle Scholar
  25. 25.
    Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, Mendoza G, Weber-Luxenburger G, Lottgen J, Thiel A, Wienhard K, Heiss WD (1998) 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology 50:1316–1322CrossRefPubMedGoogle Scholar
  26. 26.
    Beaufrere B, Horber FF, Schwenk WF et al (1989) Glucocorticosteroids increase leucine oxidation and impair leucine balance in humans. Am J Phys 257:E712–E721Google Scholar
  27. 27.
    Garrel DR, Moussali R, De Oliveira A et al (1995) RU 486 prevents the acute effects of cortisol on glucose and leucine metabolism. J Clin Endocrinol Metab 80:379–385PubMedGoogle Scholar
  28. 28.
    Schwertfeger M, Pissowotzki K, Fleck C, Taylor PM (2003) Regulation of L-leucine transport in rat kidney by dexamethasone and triiodothyronine. Amino Acids 25:75–83CrossRefPubMedGoogle Scholar
  29. 29.
    Varlamov O, Bethea CL, Roberts CT Jr (2014) Sex-specific differences in lipid and glucose metabolism. Front Endocrinol (Lausanne) 5:241Google Scholar
  30. 30.
    Clayton JA, Collins FS (2014) Policy: NIH to balance sex in cell and animal studies. Nature 509:282–283CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fuller CM, Insel PA (2014) I don’t know the question, but sex is definitely the answer! Focus on “in pursuit of scientific excellence: sex matters” and “do you know the sex of your cells?”. Am J Phys Cell Phys 306:C1–C2CrossRefGoogle Scholar
  32. 32.
    Verger A, Stegmayr C, Galldiks N, van der Gucht A, Lohmann P, Stoffels G, Shah NJ, Fink GR, Eickhoff SB, Guedj E, Langen KJ (2018) Evaluation of factors influencing 18F-FET uptake in the brain. Neuroimage Clin 17:491–497CrossRefPubMedGoogle Scholar
  33. 33.
    Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Müller HW, Coenen HH, Langen KJ (2003) Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine. Eur J Nucl Med Mol Imaging 30:519–524CrossRefPubMedGoogle Scholar

Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  1. 1.Institute of Neuroscience and Medicine (INM-3, INM-4; INM-5; INM-11), Forschungszentrum JülichJülichGermany
  2. 2.Department of NeurologyUniversity of CologneCologneGermany
  3. 3.Center of Integrated Oncology (CIO)Universities of Cologne and BonnCologneGermany
  4. 4.Jülich-Aachen Research Alliance (JARA) – Section JARA-BrainAachenGermany
  5. 5.Department of NeurologyRWTH University AachenAachenGermany
  6. 6.Department of Nuclear MedicineRWTH University Hospital AachenAachenGermany

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