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Reproducibility of O-(2-18F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Positron emission tomography (PET) using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of 18F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy.

Methods

F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10–11 days of tumor growth, the animals underwent dynamic PET after injection of 18F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of 18F-FET uptake (18–61 min p.i.) and the slope of the time-activity-curves (TAC) (18–61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC).

Results

The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (−8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC.

Conclusion

TBR of 18F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.

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References

  1. Galldiks N, Langen KJ. Applications of PET imaging of neurological tumors with radiolabeled amino acids. Q J Nucl Med Mol Imaging: Off Publ Ital Assoc Nucl Med. 2015;59:70–82.

    CAS  Google Scholar 

  2. Herholz K, Langen KJ, Schiepers C, Mountz JM. Brain tumors. Semin Nucl Med. 2012;42:356–70.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Langen KJ, Hamacher K, Weckesser M, Floeth F, Stoffels G, Bauer D, et al. O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2006;33:287–94.

    Article  CAS  PubMed  Google Scholar 

  4. Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med: Off Publ Soc Nucl Med. 1999;40:205–12.

    CAS  Google Scholar 

  5. Galldiks N, Langen K, Holy R, Pinkawa M, Stoffels G, Nolte K, et al. Assessment of treatment response in patients with glioblastoma using [18F]Fluoroethyl-L-Tyrosine PET in comparison to MRI. J Nucl Med: Off Publ Soc Nucl Med. 2012;53:1048–57.

    Article  CAS  Google Scholar 

  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: J Neurol. 2005;128:678–87.

    Article  Google Scholar 

  7. Pauleit D, Stoffels G, Bachofner A, Floeth FW, Sabel M, Herzog H, et al. Comparison of (18)F-FET and (18)F-FDG PET in brain tumors. Nucl Med Biol. 2009;36:779–87.

    Article  CAS  PubMed  Google Scholar 

  8. Pichler R, Dunzinger A, Wurm G, Pichler J, Weis S, Nussbaumer K, et al. Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance? Eur J Nucl Med Mol Imaging. 2010;37:1521–8.

    Article  PubMed  Google Scholar 

  9. Popperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)- L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004;31:1464–70.

    Article  PubMed  Google Scholar 

  10. Floeth FW, Pauleit D, Sabel M, Stoffels G, Reifenberger G, Riemenschneider MJ, et al. Prognostic value of O-(2-18F-fluoroethyl)-L-tyrosine PET and MRI in low-grade glioma. J Nucl Med: Off Publ Soc Nucl Med. 2007;48:519–27.

    Article  CAS  Google Scholar 

  11. 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: Off Publ Soc Nucl Med. 2015;56:9–15.

    Article  CAS  Google Scholar 

  12. 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: Off Publ Soc Nucl Med. 2006;47:393–403.

    Google Scholar 

  13. Weckesser M, Langen KJ, Rickert CH, Kloska S, Straeter R, Hamacher K, et al. O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging. 2005;32:422–9.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Odewole OA, Oyenuga OA, Tade F, Savir-Baruch B, Nieh PT, Master V, et al. Reproducibility and reliability of anti-3-[(1)(8)F]FACBC uptake measurements in background structures and malignant lesions on follow-up PET-CT in prostate carcinoma: an exploratory analysis. Mol Imaging Biol: Off Publ Acad Mol Imaging. 2015;17:277–83.

    Article  Google Scholar 

  17. Langen KJ, Roosen N, Coenen HH, Kuikka JT, Kuwert T, Herzog H, et al. Brain and brain tumor uptake of L-3-[123I]iodo-alpha-methyl tyrosine: competition with natural L-amino acids. J Nucl Med: Off Publ Soc Nucl Med. 1991;32:1225–9.

    CAS  Google Scholar 

  18. Piroth MD, Pinkawa M, Holy R, Klotz J, Nussen S, Stoffels G, et al. Prognostic value of early [18F]fluoroethyltyrosine positron emission tomography after radiochemotherapy in glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2011;80:176–84.

    Article  PubMed  Google Scholar 

  19. Kotsarini C, Griffiths PD, Wilkinson ID, Hoggard N. 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. 2010;67:1799–815.

    Article  PubMed  Google Scholar 

  20. Sarin R, Murthy V. Medical decompressive therapy for primary and metastatic intracranial tumours. Lancet Neurol. 2003;2:357–65.

    Article  CAS  PubMed  Google Scholar 

  21. 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;50:1316–22.

    Article  CAS  PubMed  Google Scholar 

  22. Piroth MD, Prasath J, Willuweit A, Stoffels G, Sellhaus B, van Osterhout A, et al. Uptake of O-(2-[18F]fluoroethyl)-L-tyrosine in reactive astrocytosis in the vicinity of cerebral gliomas. Nucl Med Biol. 2013;40:795–800.

    Article  CAS  PubMed  Google Scholar 

  23. Langen KJ, Jarosch M, Muhlensiepen H, Hamacher K, Broer S, Jansen P, et al. Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas. Nucl Med Biol. 2003;30:501–8.

    Article  CAS  PubMed  Google Scholar 

  24. Ewing JR, Brown SL, Nagaraja TN, Bagher-Ebadian H, Paudyal R, Panda S, et al. MRI measurement of change in vascular parameters in the 9L rat cerebral tumor after dexamethasone administration. J Magn Reson Imaging: JMRI. 2008;27:1430–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bao Q, Newport D, Chen M, Stout DB, Chatziioannou AF. Performance evaluation of the inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med: Off Publ Soc Nucl Med. 2009;50:401–8.

    Article  Google Scholar 

  26. Hamacher K, Coenen HH. Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot: Incl Data Instrum Methods Use Agric Ind Med. 2002;57:853–6.

    Article  CAS  Google Scholar 

  27. Miller JN. Basic statistical methods for Analytical Chemistry. Part 2. Calibration and regression methods. A review. Analyst. 1991;116:3–14.

    Article  CAS  Google Scholar 

  28. Galldiks N, Rapp M, Stoffels G, Dunkl V, Sabel M, Langen KJ. Earlier diagnosis of progressive disease during bevacizumab treatment using O-(2-18F-fluorethyl)-L-tyrosine positron emission tomography in comparison with magnetic resonance imaging. Mol Imaging. 2013;12:273–6.

    PubMed  Google Scholar 

  29. 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: Off Publ Soc Nucl Med. 2011;52:856–64.

    Article  CAS  Google Scholar 

  30. Popperl G, Goldbrunner R, Gildehaus FJ, Kreth FW, Tanner P, Holtmannspotter M, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma. Eur J Nucl Med Mol Imaging. 2005;32:1018–25.

    Article  CAS  PubMed  Google Scholar 

  31. Pöpperl G, Götz C, Rachinger W, Schnell O, Gildehaus FJ, Tonn JC, et al. Serial O-(2-[(18)F]fluoroethyl)-L:-tyrosine PET for monitoring the effects of intracavitary radioimmunotherapy in patients with malignant glioma. Eur J Nucl Med Mol Imaging. 2006;33:792–800.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nedergaard MK, Michaelsen SR, Urup T, Broholm H, El Ali H, Poulsen HS, et al. 18F-FET MicroPET and MicroMRI for anti-VEGF and anti-PlGF response assessment in an orthotopic murine model of human glioblastoma. PLoS One. 2015;10:e0115315.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nedergaard MK, Kristoffersen K, Michaelsen SR, Madsen J, Poulsen HS, Stockhausen MT, et al. The use of longitudinal 18F-FET MicroPET imaging to evaluate response to irinotecan in orthotopic human glioblastoma multiforme xenografts. PLoS One. 2014;9:e100009.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 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: Off Publ Soc Nucl Med. 2013;54:2046–54.

    Article  CAS  Google Scholar 

  35. 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.

    CAS  PubMed  Google Scholar 

  36. Habermeier A, Graf J, Sandhofer BF, Boissel JP, Roesch F, Closs EI. System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. 2015;47:335–44.

    Article  CAS  PubMed  Google Scholar 

  37. Lahoutte T, Caveliers V, Franken PR, Bossuyt A, Mertens J, Everaert H. Increased tumor uptake of 3-(123)I-Iodo-L-alpha-methyltyrosine after preloading with amino acids: an in vivo animal imaging study. J Nucl Med: Off Publ Soc Nucl Med. 2002;43:1201–6.

    CAS  Google Scholar 

  38. Le Cam A, Freychet P. Effect of glucocorticoids on amino acid transport in isolated rat hepatocytes. Mol Cell Endocrinol. 1977;9:205–14.

    Article  PubMed  Google Scholar 

  39. Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, et al. [F-18]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro-Oncology. 2013;15:341–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Langen KJ, Galldiks N. Reply to “[18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma” by Hutterer et al. Neuro-Oncology. 2013;15:816–7.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Christian N, Lee JA, Bol A, De Bast M, Jordan B, Gregoire V. The limitation of PET imaging for biological adaptive-IMRT assessed in animal models. Radiother Oncol: J Eur Soc Ther Radiol Oncol. 2009;91:101–6.

    Article  Google Scholar 

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Acknowledgments

The authors wish to thank Mrs. Michaela Bohlen, Mrs. Tanja Juraschek and Mrs. Larissa Damm for animal husbandry, and Mrs. Erika Wabbals, Mrs. Silke Grafmüller and Mr. Sascha Rehbein for technical assistance in radiosynthesis of 18F-FET.

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Authors and Affiliations

  1. Research Center Jülich, Institute of Neuroscience and Medicine, Jülich, Germany

    Carina Stegmayr, Michael Schöneck, Dennis Oliveira, Antje Willuweit, Christian Filss, Norbert Galldiks, N. Jon Shah, Heinz H. Coenen & Karl-Josef Langen

  2. Department of Nuclear Medicine and Neurology, University of Aachen, Aachen, Germany

    Christian Filss, N. Jon Shah, Heinz H. Coenen & Karl-Josef Langen

  3. Department of Neurology, University of Cologne, Cologne, Germany

    Norbert Galldiks

  4. Jülich-Aachen Research Alliance (JARA) – Section JARA-Brain, Jülich, Germany

    N. Jon Shah

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  1. Carina Stegmayr
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Correspondence to Karl-Josef Langen.

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Stegmayr, C., Schöneck, M., Oliveira, D. et al. 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, 1115–1123 (2016). https://doi.org/10.1007/s00259-015-3274-4

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