Positron Emission Tomography in Diffuse Low-Grade Gliomas

  • Karl-Josef LangenEmail author
  • Frank Willi Floeth
  • Michael Sabel
  • Norbert Galldiks


MRI is currently the method of choice for the diagnosis of diffuse low-grade gliomas and provides an excellent depiction of structural changes in the brain. Nevertheless, the delineation of the tumor from normal brain tissue and nonspecific abnormalities on MRI such as edema- or treatment-related changes can be difficult. Positron emission tomography (PET) provides additional information on tumor metabolism and is helpful in many clinical situations. In particular, PET using radiolabeled amino acids has a wide range of applications and helps to solve a number of clinical issues. At initial diagnosis, amino acid PET may be helpful to estimate the prognosis of a low-grade glioma and to decide on the therapeutic strategy. The method improves targeting of biopsy and provides additional information of tumor extent which is helpful for planning neurosurgery and radiotherapy. In the further course of the disease, amino acid PET allows a sensitive monitoring of treatment response, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from treatment-related changes of the brain tissue. In the past, the method had only limited availability due to the low number of PET scanners and the use of radiopharmaceuticals with a short half-life. In recent years, however, the number of PET scanners in hospitals has increased considerably. Furthermore, novel amino acid tracers labeled with positron emitters with a longer half-life have been developed and clinically validated which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that the method may be available as a routine diagnostic technique for certain indications in the near future.


Low grade glioma PET Radiolabeled amino acids C-11-methionine F18-fluoroethyltyrosine (FET) 


  1. 1.
    Wessels PH, Weber WE, Raven G, Ramaekers FC, Hopman AH, Twijnstra A. Supratentorial grade II astrocytoma: biological features and clinical course. Lancet Neurol. 2003;2(7):395–403. Epub 2003/07/10.PubMedCrossRefGoogle Scholar
  2. 2.
    Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P, et al. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol. 2002;20(8):2076–84. Epub 2002/04/17.PubMedCrossRefGoogle Scholar
  3. 3.
    Lustig RA, Seiferheld W, Berkey B, Yung AW, Scarantino C, Movsas B, et al. Imaging response in malignant glioma, RTOG 90–06. Am J Clin Oncol. 2007;30(1):32–7. Epub 2007/02/07.PubMedCrossRefGoogle Scholar
  4. 4.
    Chen W. Clinical applications of PET in brain tumors. J Nucl Med. 2007;48(9):1468–81. Epub 2007/08/21.PubMedCrossRefGoogle Scholar
  5. 5.
    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(8):1521–8. Epub 2010/04/17.PubMedCrossRefGoogle Scholar
  6. 6.
    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(5):1316–22. Epub 1998/05/22.PubMedCrossRefGoogle Scholar
  7. 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(7):779–87. Epub 2009/09/02.PubMedCrossRefGoogle Scholar
  8. 8.
    Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P, et al. Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy. J Nucl Med. 1997;38(9):1459–62. Epub 1997/09/18.PubMedGoogle Scholar
  9. 9.
    Pirotte B, Goldman S, Massager N, David P, Wikler D, Lipszyc M, et al. Combined use of 18F-fluorodeoxyglucose and 11C-methionine in 45 positron emission tomography-guided stereotactic brain biopsies. J Neurosurg. 2004;101(3):476–83. Epub 2004/09/09.PubMedCrossRefGoogle Scholar
  10. 10.
    Mosskin M, Ericson K, Hindmarsh T, von Holst H, Collins VP, Bergstrom M, et al. Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference. Acta Radiol. 1989;30(3):225–32. Epub 1989/05/01.PubMedCrossRefGoogle Scholar
  11. 11.
    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(21):7163–70. Epub 2004/11/10.PubMedCrossRefGoogle Scholar
  12. 12.
    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. Epub 2005/02/04.PubMedCrossRefGoogle Scholar
  13. 13.
    Pirotte B, Goldman S, Dewitte O, Massager N, Wikler D, Lefranc F, et al. Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures. J Neurosurg. 2006;104(2):238–53. Epub 2006/03/03.PubMedCrossRefGoogle Scholar
  14. 14.
    Singhal T, Narayanan TK, Jain V, Mukherjee J, Mantil J. 11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas. Mol Imaging Biol. 2008;10(1):1–18. Epub 2007/10/25.PubMedCrossRefGoogle Scholar
  15. 15.
    Padma MV, Said S, Jacobs M, Hwang DR, Dunigan K, Satter M, et al. Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol. 2003;64(3):227–37. Epub 2003/10/16.PubMedCrossRefGoogle Scholar
  16. 16.
    Hatakeyama T, Kawai N, Nishiyama Y, Yamamoto Y, Sasakawa Y, Ichikawa T, et al. 11C-methionine (MET) and 18F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma. Eur J Nucl Med Mol Imaging. 2008;35(11):2009–17. Epub 2008/06/11.PubMedCrossRefGoogle Scholar
  17. 17.
    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(12):1933–42. Epub 2007/09/04.PubMedCrossRefGoogle Scholar
  18. 18.
    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(3):393–403. Epub 2006/03/04.PubMedGoogle Scholar
  19. 19.
    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. 2007;48(4):519–27. Epub 2007/04/03.PubMedCrossRefGoogle Scholar
  20. 20.
    Ribom D, Eriksson A, Hartman M, Engler H, Nilsson A, Langstrom B, et al. Positron emission tomography (11)C-methionine and survival in patients with low-grade gliomas. Cancer. 2001;92(6):1541–9. Epub 2001/12/18.PubMedCrossRefGoogle Scholar
  21. 21.
    De Witte O, Goldberg I, Wikler D, Rorive S, Damhaut P, Monclus M, et al. Positron emission tomography with injection of methionine as a prognostic factor in glioma. J Neurosurg. 2001;95(5):746–50. Epub 2001/11/13.PubMedCrossRefGoogle Scholar
  22. 22.
    Ribom D, Smits A. Baseline 11C-methionine PET reflects the natural course of grade 2 oligodendrogliomas. Neurol Res. 2005;27(5):516–21. Epub 2005/06/28.PubMedGoogle Scholar
  23. 23.
    Arbizu J, Tejada S, Marti-Climent JM, Diez-Valle R, Prieto E, Quincoces G, et al. Quantitative volumetric analysis of gliomas with sequential MRI and (11)C-methionine PET assessment: patterns of integration in therapy planning. Eur J Nucl Med Mol Imaging. 2012;39(5):771–81. Epub 2012/01/20.PubMedCrossRefGoogle Scholar
  24. 24.
    Pirotte B, Levivier M, Morelli D, Van Bogaert P, Detemmerman D, David P, et al. Positron emission tomography for the early postsurgical evaluation of pediatric brain tumors. Childs Nerv Syst. 2005;21(4):294–300. Epub 2005/03/31.PubMedCrossRefGoogle Scholar
  25. 25.
    Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010;96(3):325–7. Epub 2010/08/24.PubMedCrossRefGoogle Scholar
  26. 26.
    Nuutinen J, Sonninen P, Lehikoinen P, Sutinen E, Valavaara R, Eronen E, et al. Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma. Int J Radiat Oncol Biol Phys. 2000;48(1):43–52. Epub 2000/08/05.PubMedCrossRefGoogle Scholar
  27. 27.
    Van Laere K, Ceyssens S, Van Calenbergh F, de Groot T, Menten J, Flamen P, et al. Direct comparison of 18F-FDG and 11C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value. Eur J Nucl Med Mol Imaging. 2005;32(1):39–51. Epub 2004/08/17.PubMedCrossRefGoogle Scholar
  28. 28.
    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(11):1464–70. Epub 2004/07/13.PubMedCrossRefGoogle Scholar
  29. 29.
    Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med. 2008;49(5):694–9. Epub 2008/04/17.PubMedCrossRefGoogle Scholar
  30. 30.
    Roelcke U, von Ammon K, Hausmann O, Kaech DL, Vanloffeld W, Landolt H, et al. Operated low grade astrocytomas: a long term PET study on the effect of radiotherapy. J Neurol Neurosurg Psychiatry. 1999;66:644–7. Epub 1999/04/21.PubMedCrossRefGoogle Scholar
  31. 31.
    Voges J, Herholz K, Holzer T, Würker M, Bauer B, Pietrzyk U, et al. 11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds. Stereotact Funct Neurosurg. 1997;69:129–35. Epub 1997/01/01.PubMedCrossRefGoogle Scholar
  32. 32.
    Würker M, Herholz K, Voges J, Pietrzyk U, Treuer H, Bauer B, et al. Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy. Eur J Nucl Med. 1996;23:583–6. Epub 1996/05/01.PubMedCrossRefGoogle Scholar
  33. 33.
    Wyss M, Hofer S, Bruehlmeier M, Hefti M, Uhlmann C, Bartschi E, et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol. 2009;95:87–93. Epub 2009/04/22.PubMedCrossRefGoogle Scholar
  34. 34.
    Tang BN, Sadeghi N, Branle F, De Witte O, Wikler D, Goldman S. Semi-quantification of methionine uptake and flair signal for the evaluation of chemotherapy in low-grade oligodendroglioma. J Neurooncol. 2005;71:161–8. Epub 2005/02/04.PubMedCrossRefGoogle Scholar
  35. 35.
    Smits A, Baumert BG. The clinical value of PET with amino acid tracers for gliomas WHO grade II. Int J Mol Imaging. 2011;2011:372509. Epub 2011/05/24.PubMedGoogle Scholar
  36. 36.
    Minn H. PET and SPECT in low-grade glioma. Eur J Radiol. 2005;56(2):171–8. Epub 2005/10/20.PubMedCrossRefGoogle Scholar
  37. 37.
    Langen KJ, Tatsch K, Grosu AL, Jacobs AH, Weckesser M, Sabri O. Diagnostics of cerebral gliomas with radiolabeled amino acids. Dtsch Arztebl Int. 2008;105(4):55–61. Epub 2008/01/01.PubMedGoogle Scholar
  38. 38.
    Derlon JM. The in vivo metabolic investigation of brain gliomas with positron emission tomography. Adv Tech Stand Neurosurg. 1998;24:41–76. Epub 1999/03/02.PubMedCrossRefGoogle Scholar
  39. 39.
    Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, et al. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med. 2005;46(6):945–52. Epub 2005/06/07.PubMedGoogle Scholar
  40. 40.
    Price SJ, Fryer TD, Cleij MC, Dean AF, Joseph J, Salvador R, et al. Imaging regional variation of cellular proliferation in gliomas using 3′-deoxy-3′-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study. Clin Radiol. 2009;64(1):52–63. Epub 2008/12/17.PubMedCrossRefGoogle Scholar
  41. 41.
    Jacobs AH, Thomas A, Kracht LW, Li H, Dittmar C, Garlip G, et al. 18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med. 2005;46(12):1948–58. Epub 2005/12/07.PubMedGoogle Scholar
  42. 42.
    Ohtani T, Kurihara H, Ishiuchi S, Saito N, Oriuchi N, Inoue T, et al. Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur J Nucl Med. 2001;28(11):1664–70. Epub 2001/11/10.PubMedCrossRefGoogle Scholar
  43. 43.
    Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, et al. Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys. 1992;22(1):199–212. Epub 1992/01/01.PubMedCrossRefGoogle Scholar
  44. 44.
    Cher LM, Murone C, Lawrentschuk N, Ramdave S, Papenfuss A, Hannah A, et al. Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med. 2006;47(3):410–8. Epub 2006/03/04.PubMedGoogle Scholar
  45. 45.
    Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42(3):432–45. Epub 2001/05/05.PubMedGoogle Scholar
  46. 46.
    Ishiwata K, Kubota K, Murakami M, Kubota R, Sasaki T, Ishii S, et al. Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo? J Nucl Med. 1993;34(11):1936–43. Epub 1993/11/01.PubMedGoogle Scholar
  47. 47.
    Wienhard K, Herholz K, Coenen HH, Rudolf J, Kling P, Stocklin G, et al. Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine. J Nucl Med. 1991;32(7):1338–46. Epub 1991/07/01.PubMedGoogle Scholar
  48. 48.
    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(3):287–94. Epub 2006/04/25.PubMedCrossRefGoogle Scholar
  49. 49.
    Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, et al. O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study. Eur J Nucl Med. 2000;27(5):542–9. Epub 2000/06/15.PubMedCrossRefGoogle Scholar
  50. 50.
    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(5):501–8. Epub 2003/07/02.PubMedCrossRefGoogle Scholar
  51. 51.
    Grosu AL, Astner ST, Riedel E, Nieder C, Wiedenmann N, Heinemann F, et al. An Interindividual Comparison of O-(2- [(18)F]Fluoroethyl)-L-Tyrosine (FET)- and L-[Methyl-(11)C]Methionine (MET)-PET in Patients With Brain Gliomas and Metastases. Int J Radiat Oncol Biol Phys. 2011;81(4):1049–58. Epub 2011/05/17.PubMedCrossRefGoogle Scholar
  52. 52.
    Becherer A, Karanikas G, Szabo M, Zettinig G, Asenbaum S, Marosi C, et al. Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine. Eur J Nucl Med Mol Imaging. 2003;30(11):1561–7. Epub 2003/10/28.PubMedCrossRefGoogle Scholar
  53. 53.
    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. 1999;40(1):205–12. Epub 1999/02/06.PubMedGoogle Scholar
  54. 54.
    Hamacher K, Coenen HH. Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot. 2002;57(6):853–6. Epub 2002/10/31.PubMedCrossRefGoogle Scholar
  55. 55.
    Salber D, Stoffels G, Oros-Peusquens AM, Shah NJ, Reifenberger G, Hamacher K, et al. Comparison of O-(2-18F-fluoroethyl)-L-tyrosine and L-3H-methionine uptake in cerebral hematomas. J Nucl Med. 2010;51(5):790–7. Epub 2010/04/17.PubMedCrossRefGoogle Scholar
  56. 56.
    Salber D, Stoffels G, Pauleit D, Oros-Peusquens AM, Shah NJ, Klauth P, et al. Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses. J Nucl Med. 2007;48(12):2056–62. Epub 2007/11/17.PubMedCrossRefGoogle Scholar
  57. 57.
    Salber D, Stoffels G, Pauleit D, Reifenberger G, Sabel M, Shah NJ, et al. Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia. Nucl Med Biol. 2006;33(8):1029–35. Epub 2006/11/28.PubMedCrossRefGoogle Scholar
  58. 58.
    Floeth FW, Pauleit D, Sabel M, Reifenberger G, Stoffels G, Stummer W, et al. 18F-FET PET differentiation of ring-enhancing brain lesions. J Nucl Med. 2006;47(5):776–82. Epub 2006/04/29.PubMedGoogle Scholar
  59. 59.
    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(6):868–73. Epub 2003/04/15.PubMedCrossRefGoogle Scholar
  60. 60.
    Stockhammer F, Plotkin M, Amthauer H, van Landeghem FK, Woiciechowsky C. Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrast-enhancing gliomas. J Neurooncol. 2008;88(2):205–10. Epub 2008/03/05.PubMedCrossRefGoogle Scholar
  61. 61.
    Okita Y, Kinoshita M, Goto T, Kagawa N, Kishima H, Shimosegawa E, et al. (11)C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: a stereotactic image-histology comparison. Neuroimage. 2010;49(4):2977–82. Epub 2009/11/26.PubMedCrossRefGoogle Scholar
  62. 62.
    Stiver SI. Angiogenesis and its role in the behavior of astrocytic brain tumors. Front Biosci. 2004;9:3105–23. Epub 2004/09/09.PubMedCrossRefGoogle Scholar
  63. 63.
    Floeth FW, Sabel M, Ewelt C, Stummer W, Felsberg J, Reifenberger G, et al. Comparison of (18)F-FET PET and 5-ALA fluorescence in cerebral gliomas. Eur J Nucl Med Mol Imaging. 2011;38(4):731–41. Epub 2010/12/15.PubMedCrossRefGoogle Scholar
  64. 64.
    Levivier M, Massager N, Wikler D, Lorenzoni J, Ruiz S, Devriendt D, et al. Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification. J Nucl Med. 2004;45(7):1146–54. Epub 2004/07/06.PubMedGoogle Scholar
  65. 65.
    Grosu AL, Weber WA, Franz M, Stark S, Piert M, Thamm R, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63(2):511–9. Epub 2005/09/20.PubMedCrossRefGoogle Scholar
  66. 66.
    Rickhey M, Koelbl O, Eilles C, Bogner L. A biologically adapted dose-escalation approach, demonstrated for 18F-FET-PET in brain tumors. Strahlenther Onkol. 2008;184(10):536–42. Epub 2008/11/19.PubMedCrossRefGoogle Scholar
  67. 67.
    Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, et al. [(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma. Radiat Oncol. 2008;3:44. Epub 2008/12/26.PubMedCrossRefGoogle Scholar
  68. 68.
    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. Epub 2009/11/26.PubMedCrossRefGoogle Scholar
  69. 69.
    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(4):422–9. Epub 2005/01/15.PubMedCrossRefGoogle Scholar
  70. 70.
    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(3):307–16. Epub 2011/02/05.PubMedCrossRefGoogle Scholar
  71. 71.
    Moulin-Romsee G, D’Hondt E, de Groot T, Goffin J, Sciot R, Mortelmans L, et al. Non-invasive grading of brain tumours using dynamic amino acid PET imaging: does it work for 11C-methionine? Eur J Nucl Med Mol Imaging. 2007;34(12):2082–7. Epub 2007/09/04.PubMedCrossRefGoogle Scholar
  72. 72.
    Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del Fiore G, et al. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med. 1998;39(5):778–85. Epub 1998/05/20.PubMedGoogle Scholar
  73. 73.
    Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22(6):633–8. Epub 2009/09/23.PubMedCrossRefGoogle Scholar
  74. 74.
    Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP. Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? AJNR Am J Neuroradiol. 1998;19(3):407–13. Epub 1998/04/16.PubMedGoogle Scholar
  75. 75.
    Rachinger W, Goetz C, Popperl G, Gildehaus FJ, Kreth FW, Holtmannspotter M, et al. Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery. 2005;57(3):505–11; discussion 505−11. Epub 2005/09/08.PubMedCrossRefGoogle Scholar
  76. 76.
    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(1):176–84. Epub 2010/07/22.PubMedCrossRefGoogle Scholar
  77. 77.
    Galldiks N, Kracht LW, Burghaus L, Thomas A, Jacobs AH, Heiss WD, et al. Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging. 2006;33(5):516–24. Epub 2006/02/02.PubMedCrossRefGoogle Scholar
  78. 78.
    Herholz K, Kracht LW, Heiss WD. Monitoring the effect of chemotherapy in a mixed glioma by C-11-methionine PET. J Neuroimaging. 2003;13(3):269–71. Epub 2003/08/02.PubMedGoogle Scholar
  79. 79.
    Galldiks N, Kracht LW, Burghaus L, Ullrich RT, Backes H, Brunn A, et al. Patient-tailored, imaging-guided, long-term temozolomide chemotherapy in patients with glioblastoma. Mol Imaging. 2010;9:40–6. Epub 2010/02/05.PubMedGoogle Scholar
  80. 80.
    Popperl G, Gotz 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(7):792–800. Epub 2006/03/22.PubMedCrossRefGoogle Scholar
  81. 81.
    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(9):1018–25. Epub 2005/05/07.PubMedCrossRefGoogle Scholar
  82. 82.
    Galldiks N, Ullrich R, Schroeter M, Fink GR, Kracht LW. Imaging biological activity of a glioblastoma treated with an individual patient-tailored, experimental therapy regimen. J Neurooncol. 2009;93:425–30. Epub 2009/02/03.PubMedCrossRefGoogle Scholar
  83. 83.
    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. Epub 2011/05/31.PubMedCrossRefGoogle Scholar
  84. 84.
    Herholz K, Coope D, Jackson A. Metabolic and molecular imaging in neuro-oncology. Lancet Neurol. 2007;6(8):711–24. Epub 2007/07/20.PubMedCrossRefGoogle Scholar
  85. 85.
    Stadlbauer A, Prante O, Nimsky C, Salomonowitz E, Buchfelder M, Kuwert T, et al. Metabolic ­imaging of cerebral gliomas: spatial correlation of changes in O-(2-18F-fluoroethyl)-L-tyrosine PET and proton magnetic resonance spectroscopic ­imaging. J Nucl Med. 2008;49(5):721–9. Epub 2008/04/17.PubMedCrossRefGoogle Scholar
  86. 86.
    Yang I, Aghi MK. New advances that enable identification of glioblastoma recurrence. Nat Rev Clin Oncol. 2009;6:648–57. Epub 2009/10/07.PubMedCrossRefGoogle Scholar
  87. 87.
    Stadlbauer A, Polking E, Prante O, Nimsky C, Buchfelder M, Kuwert T, et al. Detection of tumour invasion into the pyramidal tract in glioma patients with sensorimotor deficits by correlation of (18)F-fluoroethyl-L: -tyrosine PET and magnetic resonance diffusion tensor imaging. Acta Neurochir. 2009;151(9):1061–9. Epub 2009/05/27.PubMedCrossRefGoogle Scholar
  88. 88.
    Stadlbauer A, Hammen T, Grummich P, Buchfelder M, Kuwert T, Dorfler A, et al. Classification of peritumoral fiber tract alterations in gliomas using metabolic and structural neuroimaging. J Nucl Med. 2011;52(8):1227–34. Epub 2011/08/04.PubMedCrossRefGoogle Scholar
  89. 89.
    Van der Borght T, Asenbaum S, Bartenstein P, Halldin C, Kapucu O, 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. Epub 2006/08/26.CrossRefGoogle Scholar
  90. 90.
    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 Nuclear medicine. 2011;50(4):167–73. Epub 2011/07/27. PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosauren.PubMedCrossRefGoogle Scholar
  91. 91.
    Herzog H, Langen KJ, Weirich C, Rota Kops E, Kaffanke J, Tellmann L, et al. High resolution BrainPET combined with simultaneous MRI. Nuklearmedizin. 2011;50(2):74–82. Epub 2011/02/03.PubMedCrossRefGoogle Scholar
  92. 92.
    Rapp M et al. Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med. 2012. [Epub ahead of print] PubMed PMID: 23232275.Google Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Karl-Josef Langen
    • 1
    Email author
  • Frank Willi Floeth
    • 2
  • Michael Sabel
    • 3
  • Norbert Galldiks
    • 4
    • 5
  1. 1.INM-4: Medical Imaging PhysicsInstitute of Neuroscience and Medicine, Forschungszentrum JülichJülichGermany
  2. 2.Department of Spine and PainSt.-Vinzenz-HospitalDüsseldorfGermany
  3. 3.Department of NeurosurgeryHeinrich-Heine-UniversityDüsseldorfGermany
  4. 4.INM-3: Cognitive NeuroscienceInstitute of Neuroscience and Medicine, Forschungszentrum JülichJülichGermany
  5. 5.Department of NeurologyUniversity Hospital CologneCologneGermany

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