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Positron-Emission-Tomography in Diffuse Low-Grade Gliomas

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Diffuse Low-Grade Gliomas in Adults

Abstract

Contrast-enhanced 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 non-specific 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 optimize patient counseling. Furthermore, the method improves targeting of biopsy and provides additional information of tumor extent, which is also helpful for resection planning 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. 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.

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References

  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.

    Google Scholar 

  2. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–72.

    Google Scholar 

  3. Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, et al. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015;16(15):e534–42.

    Google Scholar 

  4. Chen W. Clinical applications of PET in brain tumors. J Nucl Med. 2007;48(9):1468–81.

    Google Scholar 

  5. 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.

    Google Scholar 

  6. 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.

    Google Scholar 

  7. Minn H. PET and SPECT in low-grade glioma. Eur J Radiol. 2005;56(2):171–8.

    Google Scholar 

  8. Langen KJ, Tatsch K, Grosu AL, Jacobs AH, Weckesser M, Sabri O. Diagnostics of cerebral gliomas with radiolabeled amino acids. Dsches Arzteblatt Int. 2008;105(4):55–61.

    Google Scholar 

  9. Herholz K, Langen KJ, Schiepers C, Mountz JM. Brain tumors. Semin Nucl Med. 2012;42(6):356–70.

    Google Scholar 

  10. 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.

    Google Scholar 

  11. Galldiks N, Langen KJ, Pope WB. From the clinician’s point of view – what is the status quo of positron emission tomography in patients with brain tumors? Neuro-Oncology. 2015;17(11):1434–44.

    Google Scholar 

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

    Google Scholar 

  13. 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 Neuro-Oncol. 2003;64(3):227–37.

    Google Scholar 

  14. Yoon JH, Kim JH, Kang WJ, Sohn CH, Choi SH, Yun TJ, et al. Grading of cerebral glioma with multiparametric MR imaging and 18F-FDG-PET: concordance and accuracy. Eur Radiol. 2014;24(2):380–9.

    Google Scholar 

  15. 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.

    Google Scholar 

  16. Collet S, Valable S, Constans JM, Lechapt-Zalcman E, Roussel S, Delcroix N, et al. [(18)F]-fluoro-L-thymidine PET and advanced MRI for preoperative grading of gliomas. NeuroImage Clin. 2015;8:448–54.

    Google Scholar 

  17. 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.

    Google Scholar 

  18. 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.

    Google Scholar 

  19. 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.

    Google Scholar 

  20. Nowosielski M, DiFranco MD, Putzer D, Seiz M, Recheis W, Jacobs AH, et al. An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-grade gliomas. PLoS One. 2014;9(4):e95830.

    Google Scholar 

  21. 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.

    Google Scholar 

  22. Sollini M, Sghedoni R, Erba PA, Cavuto S, Froio A, De Berti G et al. Diagnostic performances of [18F]fluorocholine positron emission tomography in brain tumors. Q J Nucl Med Mol Imaging. 2015 [Epub ahead of print] PubMed PMID: 26329494.

    Google Scholar 

  23. Hatazawa J. 18F-Fluorocholine PET/CT as a complementary tool in the follow-up of low-grade glioma. Eur J Nucl Med Mol Imaging. 2015;42(6):885.

    Google Scholar 

  24. Gomez-Rio M, Testart Dardel N, Santiago Chinchilla A, Rodriguez-Fernandez A, Olivares Granados G, Luque Caro R, et al. 18F-Fluorocholine PET/CT as a complementary tool in the follow-up of low-grade glioma: diagnostic accuracy and clinical utility. Eur J Nucl Med Mol Imaging. 2015;42(6):886–95.

    Google Scholar 

  25. 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.

    Google Scholar 

  26. Kobayashi H, Hirata K, Yamaguchi S, Terasaka S, Shiga T, Houkin K. Usefulness of FMISO-PET for glioma analysis. Neurol Med Chir. 2013;53(11):773–8.

    Google Scholar 

  27. Toyonaga T, Hirata K, Yamaguchi S, Hatanaka KC, Yuzawa S, Manabe O, et al. F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors. Eur J Nucl Med Mol Imaging. 2016.

    Google Scholar 

  28. Gerstner E, Zhang Z, Fink J, Muzi M, Hanna L, Greco E, et al. ACRIN 6684: assessment of tumor hypoxia in newly diagnosed GBM using 18F-FMISO PET and MRI. Clin Cancer Res. 2016;22(20):5079–86.

    Google Scholar 

  29. 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.

    Google Scholar 

  30. Winkeler A, Boisgard R, Awde AR, Dubois A, Theze B, Zheng J, et al. The translocator protein ligand [18F]DPA-714 images glioma and activated microglia in vivo. Eur J Nucl Med Mol Imaging. 2012;39(5):811–23.

    Google Scholar 

  31. Janczar K, Su Z, Raccagni I, Anfosso A, Kelly C, Durrenberger PF, et al. The 18-kDa mitochondrial translocator protein in gliomas: from the bench to bedside. Biochem Soc Trans. 2015;43(4):579–85.

    Google Scholar 

  32. Su Z, Roncaroli F, Durrenberger PF, Coope DJ, Karabatsou K, Hinz R, et al. The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study. J Nucl Med. 2015;56(4):512–7.

    Google Scholar 

  33. Roncaroli F, Su Z, Herholz K, Gerhard A, Turkheimer FE. TSPO expression in brain tumours: is TSPO a target for brain tumour imaging? Clin Transl Imaging. 2016;4:145–56.

    Google Scholar 

  34. Jensen P, Feng L, Law I, Svarer C, Knudsen GM, Mikkelsen JD, et al. TSPO imaging in glioblastoma multiforme: a direct comparison between 123I-CLINDE SPECT, 18F-FET PET, and gadolinium-enhanced MR imaging. J Nucl Med. 2015;56(9):1386–90.

    Google Scholar 

  35. Villani V, Carapella CM, Chiaravalloti A, Terrenato I, Piludu F, Vidiri A, et al. The role of PET [18F]FDOPA in evaluating low-grade glioma. Anticancer Res. 2015;35(9):5117–22.

    Google Scholar 

  36. 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.

    Google Scholar 

  37. 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.

    Google Scholar 

  38. 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.

    Google Scholar 

  39. 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.

    Google Scholar 

  40. Grosu AL, Astner ST, Riedel E, Nieder C, Wiedenmann N, Heinemann F, et al. An interindividual comparison of O-(2-[18F]Fluoroethyl)-L-tyrosine (FET)- and L-[methyl-11C]methionine (MET)-PET in patients with brain gliomas and metastases. Int J Radiat Oncol Biol Phys. 2011;81(4):1049–58.

    Google Scholar 

  41. 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.

    Google Scholar 

  42. Lapa C, Linsenmann T, Monoranu CM, Samnick S, Buck AK, Bluemel C, et al. Comparison of the amino acid tracers 18F-FET and 18F-DOPA in high-grade glioma patients. J Nucl Med. 2014;55(10):1611–6.

    Google Scholar 

  43. Kratochwil C, Combs SE, Leotta K, Afshar-Oromieh A, Rieken S, Debus J, et al. Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent brain tumors. Neuro-Oncology. 2014;16(3):434–40.

    Google Scholar 

  44. Sioka C, Fotopoulos A, Kyritsis AP. Recent advances in PET imaging for evaluation of Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2010;37(8):1594–603.

    Google Scholar 

  45. Cicone F, Filss CP, Minniti G, Rossi-Espagnet C, Papa A, Scaringi C, et al. Volumetric assessment of recurrent or progressive gliomas: comparison between F-DOPA PET and perfusion-weighted MRI. Eur J Nucl Med Mol Imaging. 2015;42(6):905–15.

    Google Scholar 

  46. Wiriyasermkul P, Nagamori S, Tominaga H, Oriuchi N, Kaira K, Nakao H, et al. Transport of 3-fluoro-L-alpha-methyl-tyrosine by tumor-upregulated L-type amino acid transporter 1: a cause of the tumor uptake in PET. J Nucl Med. 2012;53(8):1253–61.

    Google Scholar 

  47. Youland RS, Kitange GJ, Peterson TE, Pafundi DH, Ramiscal JA, Pokorny JL, et al. The role of LAT1 in 18F-DOPA uptake in malignant gliomas. J Neuro-Oncol. 2013;111(1):11–8.

    Google Scholar 

  48. 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(2):335–44.

    Google Scholar 

  49. Barollo S, Bertazza L, Watutantrige-Fernando S, Censi S, Cavedon E, Galuppini F, et al. Overexpression of L-type amino acid transporter 1 (LAT1) and 2 (LAT2): novel markers of neuroendocrine tumors. PLoS One. 2016;11(5):e0156044.

    Google Scholar 

  50. Okubo S, Zhen HN, Kawai N, Nishiyama Y, Haba R, Tamiya T. Correlation of L-methyl-11C-methionine (MET) uptake with L-type amino acid transporter 1 in human gliomas. J Neuro-Oncol. 2010;99(2):217–25.

    Google Scholar 

  51. Thon N, Kunz M, Lemke L, Jansen NL, Eigenbrod S, Kreth S, et al. Dynamic 18F-FET PET in suspected WHO grade II gliomas defines distinct biological subgroups with different clinical courses. Int J Cancer. 2015;136(9):2132–45.

    Google Scholar 

  52. 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.

    Google Scholar 

  53. 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(10):841–7.

    Google Scholar 

  54. 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(12):2046–54.

    Google Scholar 

  55. 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.

    Google Scholar 

  56. 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.

    Google Scholar 

  57. 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.

    Google Scholar 

  58. Rapp M, Heinzel A, Galldiks N, Stoffels G, Felsberg J, Ewelt C, et al. Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med. 2013;54(2):229–35.

    Google Scholar 

  59. 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(6):1021–9.

    Google Scholar 

  60. Bette S, Gempt J, Delbridge C, Kirschke JS, Schlegel J, Foerster S, et al. Prognostic value of O-(2-[18F]-Fluoroethyl)-L-tyrosine-positron emission tomography imaging for histopathologic characteristics and progression-free survival in patients with low-grade glioma. World Neurosurg. 2016;89:230–9.

    Google Scholar 

  61. 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.

    Google Scholar 

  62. 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.

    Google Scholar 

  63. 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.

    Google Scholar 

  64. Sala Q, Metellus P, Taieb D, Kaphan E, Figarella-Branger D, Guedj E. 18F-DOPA, a clinically available PET tracer to study brain inflammation? Clin Nucl Med. 2014;39(4):e283–5.

    Google Scholar 

  65. Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, et al. [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro-Oncology. 2013;15(3):341–51.

    Google Scholar 

  66. Dunet V, Rossier C, Buck A, Stupp R, Prior JO. Performance of 18F-fluoro-ethyl-tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and metaanalysis. J Nucl Med. 2012;53(2):207–14.

    Google Scholar 

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

    Google Scholar 

  68. 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.

    Google Scholar 

  69. 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 glioma – does it make sense? J Nucl Med. 2016.

    Google Scholar 

  70. 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.

    Google Scholar 

  71. 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.

    Google Scholar 

  72. 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.

    Google Scholar 

  73. 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.

    Google Scholar 

  74. 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.

    Google Scholar 

  75. Manabe O, Hattori N, Yamaguchi S, Hirata K, Kobayashi K, Terasaka S, et al. Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging. Eur J Nucl Med Mol Imaging. 2015;42(6):896–904.

    Google Scholar 

  76. Shinozaki N, Uchino Y, Yoshikawa K, Matsutani T, Hasegawa A, Saeki N, et al. Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography. J Neurosurg. 2011;114(6):1640–7.

    Google Scholar 

  77. 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.

    Google Scholar 

  78. 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 Neuro-Oncol. 2008;88(2):205–10.

    Google Scholar 

  79. 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.

    Google Scholar 

  80. Stiver SI. Angiogenesis and its role in the behavior of astrocytic brain tumors. Front Biosci. 2004;9:3105–23.

    Google Scholar 

  81. 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.

    Google Scholar 

  82. Pirotte B, Goldman S, Massager N, David P, Wikler D, Vandesteene A, et al. Comparison of 18F-FDG and 11C-methionine for PET-guided stereotactic brain biopsy of gliomas. J Nucl Med. 2004;45(8):1293–8.

    Google Scholar 

  83. 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.

    Google Scholar 

  84. Kunz M, Thon N, Eigenbrod S, Hartmann C, Egensperger R, Herms J, et al. Hot spots in dynamic 18FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neuro-Oncology. 2011;13(3):307–16.

    Google Scholar 

  85. 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.

    Google Scholar 

  86. 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.

    Google Scholar 

  87. 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(Pt 3):678–87.

    Google Scholar 

  88. Lopez WO, Cordeiro JG, Albicker U, Doostkam S, Nikkhah G, Kirch RD, et al. Correlation of 18F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool. OncoTargets Ther. 2015;8:3803–15.

    Google Scholar 

  89. Floeth FW, Sabel M, Ewelt C, Stummer W, Felsberg J, Reifenberger G, et al. Comparison of 18F-FET PET and 5-ALA fluorescence in cerebral gliomas. Eur J Nucl Med Mol Imaging. 2011;38(4):731–41.

    Google Scholar 

  90. 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.

    Google Scholar 

  91. 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 11C-methionine PET assessment: patterns of integration in therapy planning. Eur J Nucl Med Mol Imaging. 2012;39(5):771–81.

    Google Scholar 

  92. Buchmann N, Klasner B, Gempt J, Bauer JS, Pyka T, Delbridge C, et al. 18F-Fluoroethyl-l-thyrosine positron emission tomography to delineate tumor residuals after glioblastoma resection: a comparison with standard postoperative magnetic resonance imaging. World Neurosurg. 2016;89:420–6.

    Google Scholar 

  93. Klasner B, Buchmann N, Gempt J, Ringel F, Lapa C, Krause BJ. Early [18F]FET-PET in gliomas after surgical resection: comparison with MRI and histopathology. PLoS One. 2015;10(10):e0141153.

    Google Scholar 

  94. Grosu AL, Weber WA. PET for radiation treatment planning of brain tumours. Radiother Oncol. 2010;96(3):325–7.

    Google Scholar 

  95. 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.

    Google Scholar 

  96. 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.

    Google Scholar 

  97. 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.

    Google Scholar 

  98. Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, et al. [18F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma. Radiat Oncol. 2008;3:44.

    Google Scholar 

  99. 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.

    Google Scholar 

  100. Munck Af Rosenschold P, Costa J, Engelholm SA, Lundemann MJ, Law I, Ohlhues L, et al. Impact of [18F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma. Neuro-Oncology. 2015;17(5):757–63.

    Google Scholar 

  101. Rieken S, Habermehl D, Giesel FL, Hoffmann C, Burger U, Rief H, et al. Analysis of FET-PET imaging for target volume definition in patients with gliomas treated with conformal radiotherapy. Radiother Oncol. 2013;109(3):487–92.

    Google Scholar 

  102. Piroth MD, Pinkawa M, Holy R, Klotz J, Schaar S, Stoffels G, et al. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study. Strahlenther Onkol. 2012;188(4):334–9.

    Google Scholar 

  103. Kosztyla R, Chan EK, Hsu F, Wilson D, Ma R, Cheung A, et al. High-grade glioma radiation therapy target volumes and patterns of failure obtained from magnetic resonance imaging and 18F-FDOPA positron emission tomography delineations from multiple observers. Int J Radiat Oncol Biol Phys. 2013;87(5):1100–6.

    Google Scholar 

  104. 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.

    Google Scholar 

  105. Dunet V, Pomoni A, Hottinger A, Nicod-Lalonde M, Prior JO. Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis. Neuro-Oncology. 2016;18(3):426–34.

    Google Scholar 

  106. Janvier L, Olivier P, Blonski M, Morel O, Vignaud JM, Karcher G, et al. Correlation of SUV-derived indices with tumoral aggressiveness of gliomas in static 18F-FDOPA PET: use in clinical practice. Clin Nucl Med. 2015;40(9):e429–35.

    Google Scholar 

  107. Pöpperl 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.

    Google Scholar 

  108. Albert NL, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E, et al. Early static 18F-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.

    Google Scholar 

  109. 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.

    Google Scholar 

  110. 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.

    Google Scholar 

  111. 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.

    Google Scholar 

  112. 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.

    Google Scholar 

  113. Pyka T, Gempt J, Hiob D, Ringel F, Schlegel J, Bette S, et al. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas. Eur J Nucl Med Mol Imaging. 2016;43(1):133–41.

    Google Scholar 

  114. Ribom D, Eriksson A, Hartman M, Engler H, Nilsson A, Langstrom B, et al. Positron emission tomography 11C-methionine and survival in patients with low-grade gliomas. Cancer. 2001;92(6):1541–9.

    Google Scholar 

  115. 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.

    Google Scholar 

  116. Pyka T, Gempt J, Ringel F, Huttinger S, van Marwick S, Nekolla S, et al. Prediction of glioma recurrence using dynamic 18F-fluoroethyltyrosine PET. AJNR Am J Neuroradiol. 2014;35(10):1924–9.

    Google Scholar 

  117. Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22(6):633–8.

    Google Scholar 

  118. 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.

    Google Scholar 

  119. Li Z, Yu Y, Zhang H, Xu G, Chen L. A meta-analysis comparing 18F-FLT PET with 18F-FDG PET for assessment of brain tumor recurrence. Nucl Med Commun. 2015;36(7):695–701.

    Google Scholar 

  120. 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.

    Google Scholar 

  121. Nihashi T, Dahabreh IJ, Terasawa T. Diagnostic accuracy of PET for recurrent glioma diagnosis: a meta-analysis. AJNR Am J Neuroradiol. 2013;34(5):944–50. S1-11

    Google Scholar 

  122. 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.

    Google Scholar 

  123. 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-Oncology. 2015;17(9):1293–300.

    Google Scholar 

  124. 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.

    Google Scholar 

  125. 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.

    Google Scholar 

  126. 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.

    Google Scholar 

  127. Popperl G, Gotz C, Rachinger W, Schnell O, Gildehaus FJ, Tonn JC, et al. Serial O-(2-[18F]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.

    Google Scholar 

  128. 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.

    Google Scholar 

  129. 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 Neuro-Oncol. 2009;93:425–30.

    Google Scholar 

  130. 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(3):137–47.

    Google Scholar 

  131. 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.

    Google Scholar 

  132. 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.

    Google Scholar 

  133. Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Grogan T, et al. Treatment response evaluation using 18F-FDOPA PET in patients with recurrent malignant glioma on bevacizumab therapy. Clin Cancer Res. 2014;20(13):3550–9.

    Google Scholar 

  134. 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 Neuosurg Psychiatry. 1999;66:644–7.

    Google Scholar 

  135. 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.

    Google Scholar 

  136. 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.

    Google Scholar 

  137. 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 Neuro-Oncol. 2009;95:87–93.

    Google Scholar 

  138. Roelcke U, Wyss MT, Nowosielski M, Ruda 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-Oncology. 2015;18(5):744–51.

    Google Scholar 

  139. 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 Neuro-Oncol. 2005;71:161–8.

    Google Scholar 

  140. Herholz K, Coope D, Jackson A. Metabolic and molecular imaging in neuro-oncology. Lancet Neurol. 2007;6(8):711–24.

    Google Scholar 

  141. Fouke SJ, Benzinger T, Gibson D, Ryken TC, Kalkanis SN, Olson JJ. The role of imaging in the management of adults with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2015;125(3):457–79.

    Google Scholar 

  142. 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 18F-fluoroethyl-L: -tyrosine PET and magnetic resonance diffusion tensor imaging. Acta Neurochir. 2009;151(9):1061–9.

    Google Scholar 

  143. 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.

    Google Scholar 

  144. Neuschmelting V, Weiss Lucas C, Stoffels G, Oros-Peusquens AM, Lockau H, Shah NJ, et al. Multimodal imaging in malignant brain tumors: enhancing the preoperative risk evaluation for motor deficits with a combined hybrid MRI-PET and navigated transcranial magnetic stimulation approach. AJNR Am J Neuroradiol. 2016;37(2):266–73.

    Google Scholar 

  145. Filss CP, Galldiks N, Stoffels G, Sabel M, Wittsack HJ, Turowski B, et al. Comparison of 18F-FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med. 2014;55(4):540–5.

    Google Scholar 

  146. Herzog H, Langen KJ, Weirich C, Rota Kops E, Kaffanke J, Tellmann L, et al. High resolution brain PET combined with simultaneous MRI. Nuklearmedizin Nucl Med. 2011;50(2):74–82.

    Google Scholar 

  147. Shah NJ, Oros-Peusquens AM, Arrubla J, Zhang K, Warbrick T, Mauler J, et al. Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T. J Magn Reson. 2013;229:101–15.

    Google Scholar 

  148. Neuner I, Kaffanke JB, Langen KJ, Kops ER, Tellmann L, Stoffels G, et al. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment. Eur Radiol. 2012;22(12):2568–80.

    Google Scholar 

  149. Heinzel A, Stock S, Langen KJ, Muller D. Cost-effectiveness analysis of FET PET-guided target selection for the diagnosis of gliomas. Eur J Nucl Med Mol Imaging. 2012;39(7):1089–96.

    Google Scholar 

  150. Vander 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.

    Google Scholar 

  151. 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 Nucl Med. 2011;50(4):167–73.

    Google Scholar 

  152. Langen KJ, Tonn JC, Weller M, Galldiks N. Letter to the Editor: “The role of imaging in the management of progressive glioblastoma. A systematic review and evidence-based clinical practice guideline” [J. Neurooncol. 2014; 118: 435–460]. J Neuro-Oncol. 2014;120(3):665–6.

    Google Scholar 

  153. Swissmedic. Swiss agency for therapeutic products. J Swissmedic. 2014;13:651.

    Google Scholar 

  154. Misch M, Guggemos A, Driever PH, Koch A, Grosse F, Steffen IG, et al. 18F-FET-PET guided surgical biopsy and resection in children and adolescence with brain tumors. Child’s Nerv Syst. 2015;31(2):261–7.

    Google Scholar 

  155. Ribom D, Smits A. Baseline 11C-methionine PET reflects the natural course of grade 2 oligodendrogliomas. Neurol Res. 2005;27(5):516–21.

    Google Scholar 

  156. 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. Child’s Nerv Syst. 2005;21(4):294–300.

    Google Scholar 

  157. 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.

    Google Scholar 

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Langen, KJ., Rapp, M., Sabel, M., Galldiks, N. (2017). Positron-Emission-Tomography in Diffuse Low-Grade Gliomas. In: Duffau, H. (eds) Diffuse Low-Grade Gliomas in Adults. Springer, Cham. https://doi.org/10.1007/978-3-319-55466-2_15

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