PET Imaging of Brain Tumors

  • Karl-Josef Langen
  • Norbert Galldiks
Part of the Medical Radiology book series (MEDRAD)


Routine diagnostics and treatment monitoring of brain tumors is usually based on magnetic resonance imaging (MRI), but the capacity of conventional MRI to differentiate tumor tissue from nonspecific tissue changes may be limited especially after therapeutic interventions such as neurosurgical resection, radiotherapy, and chemotherapy. Molecular imaging using positron-emission tomography (PET) may provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. In the last decades, a variety of molecular targets have been addressed by specific PET tracers, but only a few have achieved relevance in routine clinical practice. This book chapter is focussed on PET tracers that appear to be especially helpful in clinical decision-making with regard to a better delineation of brain tumors, prognosis, and grading, improved differentiation of tumor recurrence from nonspecific posttherapeutic changes, and treatment monitoring.


Conventional Magnetic Resonance Imaging Amino Acid Uptake Meet Uptake Cerebral Glioma Radiolabeled Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Positron-emission tomography


Magnetic resonance imaging








Blood-brain barrier






High-grade gliomas


Low-grade gliomas


  1. Afshar-Oromieh A, Giesel FL, Linhart HG, Haberkorn U, Haufe S, Combs SE, Podlesek D, Eisenhut M, Kratochwil C (2012) Detection of cranial meningiomas: comparison of (6)(8)Ga-DOTATOC PET/CT and contrast-enhanced MRI. Eur J Nucl Med Mol Imaging 39:1409–1415PubMedCrossRefGoogle Scholar
  2. Arbizu J, Tejada S, Marti-Climent JM, Diez-Valle R, Prieto E, Quincoces G, Vigil C, Idoate MA, Zubieta JL, Penuelas I, Richter JA (2012) 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 5:771–781CrossRefGoogle Scholar
  3. Bading JR, Shields AF (2008) Imaging of cell proliferation: status and prospects. J Nucl Med (official publication) 49(Suppl 2):64S–80SGoogle Scholar
  4. Basu S, Alavi A (2009) Molecular imaging (PET) of brain tumors. Neuroimaging Clin N Am 19:625–646PubMedCrossRefGoogle Scholar
  5. Becherer A, Karanikas G, Szabo M, Zettinig G, Asenbaum S, Marosi C, Henk C, Wunderbaldinger P, Czech T, Wadsak W, Kletter K (2003) Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine. Eur J Nucl Med Mol Imaging 30:1561–1567PubMedCrossRefGoogle Scholar
  6. Belohlavek O, Simonova G, Kantorova I, Novotny J Jr, Liscak R (2003) Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumour progression? Eur J Nucl Med Mol Imaging 30:96–100PubMedCrossRefGoogle Scholar
  7. Bergmann R, Pietzsch J, Fuechtner F, Pawelke B, Beuthien-Baumann B, Johannsen B, Kotzerke J (2004) 3-O–methyl-6-18F-fluoro-Ldopa, a new tumor imaging agent: investigation of transport mechanism in vitro. J Nucl Med (official publication) 45:2116–2122Google Scholar
  8. Borbely K, Nyary I, Toth M, Ericson K, Gulyas B (2006) Optimization of semi-quantification in metabolic PET studies with 18F-fluorodeoxyglucose and 11C-methionine in the determination of malignancy of gliomas. J Neurol Sci 246:85–94PubMedCrossRefGoogle Scholar
  9. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461PubMedCrossRefGoogle Scholar
  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 36:841–847PubMedCrossRefGoogle Scholar
  11. Ceyssens S, Van Laere K, de Groot T, Goffin J, Bormans G, Mortelmans L (2006) [11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence. AJNR Am J Neuroradiology 27:1432–1437Google Scholar
  12. Chen W (2007) Clinical applications of PET in brain tumors. J Nucl Med (official publication) 48:1468–1481Google Scholar
  13. Chen W, Geist C, Czernin J, Silverman D, Satyamurthy N, Delaloye S, Lai A, Phelps M, Cloughesy T (2008) Assess treatment response using FDOPA PET in patients with recurrent malignant gliomas treated with bevacizumab and irinotecan. J Nucl Med (official publication) 49(Supplement):78Google Scholar
  14. Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, Mischel P, Czernin J, Phelps ME, Silverman DH (2005) Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med (official publication) 46:945–952Google Scholar
  15. Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, Satyamurthy N, Pope W, Lai A, Phelps ME, Cloughesy T (2007) Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol 25:4714–4721PubMedCrossRefGoogle Scholar
  16. Choi SJ, Kim JS, Kim JH, Oh SJ, Lee JG, Kim CJ, Ra YS, Yeo JS, Ryu JS, Moon DH (2005) [18F]30-deoxy-30-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging 32:653–659PubMedCrossRefGoogle Scholar
  17. Crippa F, Alessi A, Serafini GL (2012) PET with radiolabeled aminoacid. Q J Nucl Med Mol Imaging 56:151–162PubMedGoogle Scholar
  18. Delbeke D, Meyerowitz C, Lapidus RL, Maciunas RJ, Jennings MT, Moots PL, Kessler RM (1995) Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. Radiology 195:47–52PubMedCrossRefGoogle Scholar
  19. Di Chiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32:1323–1329PubMedCrossRefGoogle Scholar
  20. Dooms GC, Hecht S, Brant-Zawadzki M, Berthiaume Y, Norman D, Newton TH (1986) Brain radiation lesions: MR imaging. Radiology 158:149–155PubMedCrossRefGoogle Scholar
  21. Dunet V, Rossier C, Buck A, Stupp R, Prior JO (2012) 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 (official publication) 53:207–214CrossRefGoogle Scholar
  22. Floeth FW, Pauleit D, Sabel M, Reifenberger G, Stoffels G, Stummer W, Rommel F, Hamacher K, Langen KJ (2006) 18F-FET PET differentiation of ring-enhancing brain lesions. J Nucl Med (official publication) 47:776–782Google Scholar
  23. 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 (official publication) 48:519–527Google Scholar
  24. Galldiks N, Kracht LW, Burghaus L, Thomas A, Jacobs AH, Heiss WD, Herholz K (2006) Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging 33:516–524PubMedCrossRefGoogle Scholar
  25. Galldiks N, Kracht LW, Burghaus L, Ullrich RT, Backes H, Brunn A, Heiss WD, Jacobs AH (2010a) Patient-tailored, imaging-guided, long-term temozolomide chemotherapy in patients with glioblastoma. Mol Imaging 9:40–46PubMedGoogle Scholar
  26. Galldiks N, Kracht LW, Berthold F, Miletic H, Klein JC, Herholz K, Jacobs AH, Heiss WD (2010b) [11C]-L-methionine positron emission tomography in the management of children and young adults with brain tumors. J Neurooncol 96:231–239PubMedCrossRefPubMedCentralGoogle Scholar
  27. Galldiks N, Rapp M, Stoffels G, Fink GR, Shah NJ, Coenen HH, Sabel M, Langen KJ (2013) Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-Ltyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging 40:22–33PubMedCrossRefGoogle Scholar
  28. Galldiks N, von Tempelhoff W, Kahraman D, Kracht LW, Vollmar S, Fink GR, Schroeter M, Goldbrunner R, Schmidt M, Maarouf M (2012a) 11C-methionine positron emission tomographic imaging of biologic activity of a recurrent glioblastoma treated with stereotaxy-guided laser-induced interstitial thermotherapy. Mol Imaging 11:265–271PubMedGoogle Scholar
  29. Galldiks N, Stoffels G, Filss CP, Piroth MD, Sabel M, Ruge MI, Herzog H, Shah NJ, Fink GR, Coenen HH, Langen KJ (2012b) Role of O–(2-(18)F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. J Nucl Med (official publication) 53:1367–1374Google Scholar
  30. Galldiks N, Langen K, Holy R, Pinkawa M, Stoffels G, Nolte K, Kaiser H, Filss C, Fink G, Coenen H, Eble M, Piroth M (2012c) Assessment of treatment response in patients with glioblastoma using [18F]Fluoroethyl-L-Tyrosine PET in comparison to MRI. J Nucl Med (official publication) 53:1048–1057CrossRefGoogle Scholar
  31. Gehler B, Paulsen F, Oksuz MO, Hauser TK, Eschmann SM, Bares R, Pfannenberg C, Bamberg M, Bartenstein P, Belka C, Ganswindt U (2009) [68 Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning. Radiat Oncol 4:56Google Scholar
  32. Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P, Dethy S, Brotchi J, Hildebrand J (1997) Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy. J Nucl Med (official publication) 38:1459–1462Google Scholar
  33. Graf R, Nyuyki F, Steffen IG, Michel R, Fahdt D, Wust P, Brenner W, Budach V, Wurm R, Plotkin M (2013) Contribution of 68 Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy. Int J Radiat Oncol Biol Phys 85:68–73PubMedCrossRefGoogle Scholar
  34. Grosu AL, Weber WA (2010) PET for radiation treatment planning of brain tumours. Radiother Oncol J Eur Soc Ther Radiol Oncol 96:325–327CrossRefGoogle Scholar
  35. Grosu AL, Weber WA, Franz M, Stark S, Piert M, Thamm R, Gumprecht H, Schwaiger M, Molls M, Nieder C (2005) 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 63:511–519PubMedCrossRefGoogle Scholar
  36. Grosu AL, Astner ST, Riedel E, Nieder C, Wiedenmann N, Heinemann F, Schwaiger M, Molls M, Wester HJ, Weber WA (2011) 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 81:1049–1058PubMedCrossRefGoogle Scholar
  37. Gulyas B, Halldin C (2012) New PET radiopharmaceuticals beyond FDG for brain tumor imaging. Q J Nucl Med Mol Imaging 56:173–190PubMedGoogle Scholar
  38. Gulyas B, Nyary I, Borbely K (2008) FDG, MET or CHO? The quest for the optimal PET tracer for glioma imaging continues. Nat clin pract Neurol 4:470–471PubMedCrossRefGoogle Scholar
  39. Harris RJ, Cloughesy TF, Pope WB, Nghiemphu PL, Lai A, Zaw T, Czernin J, Phelps ME, Chen W, Ellingson BM (2012) 18F-FDOPA and 18F-FLT positron emission tomography parametric response maps predict response in recurrent malignant gliomas treated with bevacizumab. Neurooncol 14:1079–1089Google Scholar
  40. Haubner R, Beer AJ, Wang H, Chen X (2010) Positron emission tomography tracers for imaging angiogenesis. Eur J Nucl Med Mol Imaging 37(Suppl 1):S86–S103PubMedCrossRefPubMedCentralGoogle Scholar
  41. Heinzel A, Stock S, Langen KJ, Muller D (2012a) Cost-effectiveness analysis of FET PET-guided target selection for the diagnosis of gliomas. Eur J Nucl Med Mol Imaging 39:1089–1096PubMedCrossRefGoogle Scholar
  42. Heinzel A, Stock S, Langen KJ, Muller D (2012b) Cost-effectiveness analysis of amino acid PET-guided surgery for supratentorial highgrade gliomas. J Nucl Med (official publication) 53:552–558Google Scholar
  43. Heinzel A, Muller D, Langen KJ, Blaum M, Verburg FA, Mottaghy FM, Galldiks N (2013) The use of O–(2-18F-Fluoroethyl)-Ltyrosine PET for treatment management of bevacizumab and irinotecan in patients with recurrent high-grade glioma: a costeffectiveness analysis. J Nucl Med (official publication) 54:1217–1222Google Scholar
  44. Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, Macke HR, Eisenhut M, Debus J, Haberkorn U (2005) Characterization of 68 Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med (official publication) 46:763–769Google Scholar
  45. Herholz K, Langen KJ, Schiepers C, Mountz JM (2012) Brain tumors. Semin Nucl Med 42:356–370PubMedCrossRefPubMedCentralGoogle Scholar
  46. 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 50:1316–1322PubMedCrossRefGoogle Scholar
  47. Horky LL, Hsiao EM, Weiss SE, Drappatz J, Gerbaudo VH (2011) Dual phase FDG-PET imaging of brain metastases provides superior assessment of recurrence versus post-treatment necrosis. J Neurooncol 103:137–146PubMedCrossRefGoogle Scholar
  48. Huang C, McConathy J (2013) Radiolabeled amino acids for oncologic imaging. J Nucl Med (official publication) 54:1007–1010Google Scholar
  49. Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H, Muigg A, Virgolini IJ, Staffen W, Trinka E, Gotwald T, Jacobs AH, Stockhammer G (2011) O–(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med (official publication) 52:856–864Google Scholar
  50. Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, McCoy M, Gobel G, la Fougere C, Virgolini IJ, Trinka E, Jacobs AH, Stockhammer G (2013) [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neurooncol 15:341–351Google Scholar
  51. Jacobs AH, Thomas A, Kracht LW, Li H, Dittmar C, Garlip G, Galldiks N, Klein JC, Sobesky J, Hilker R, Vollmar S, Herholz K, Wienhard K, Heiss WD (2005) 18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med (official publication) 46:1948–1958Google Scholar
  52. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA (2001) Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med (official publication) 42:432–445Google Scholar
  53. Jansen NL, Graute V, Armbruster L, Suchorska B, Lutz J, Eigenbrod S, Cumming P, Bartenstein P, Tonn JC, Kreth FW, la Fougere C (2012) MRI-suspected low-grade glioma: is there a need to perform dynamic FET PET? Eur J Nucl Med Mol Imaging 39:1021–1029PubMedCrossRefGoogle Scholar
  54. Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del Fiore G, Luxen A, Reznik M (1998) Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med (official publication) 39:778–785Google Scholar
  55. Kato T, Shinoda J, Nakayama N, Miwa K, Okumura A, Yano H, Yoshimura S, Maruyama T, Muragaki Y, Iwama T (2008) Metabolic assessment of gliomas using 11C-methionine, [18F] fluorodeoxyglucose, and 11C-choline positron-emission tomography. AJNR Am J Neuroradiology 29:1176–1182CrossRefGoogle Scholar
  56. Kim S, Chung JK, Im SH, Jeong JM, Lee DS, Kim DG, Jung HW, Lee MC (2005) 11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 32:52–59PubMedCrossRefGoogle Scholar
  57. Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, Klein JC, Herholz K, Heiss WD (2004) Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res J Am Assoc Cancer Res (official) 10:7163–7170Google Scholar
  58. Kunz M, Thon N, Eigenbrod S, Hartmann C, Egensperger R, Herms J, Geisler J, la Fougere C, Lutz J, Linn J, Kreth S, von Deimling A, Tonn JC, Kretzschmar HA, Pöpperl G, Kreth FW (2011a) Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neurooncol 13:307–316Google Scholar
  59. Kunz M, Thon N, Eigenbrod S, Hartmann C, Egensperger R, Herms J, Geisler J, la Fougere C, Lutz J, Linn J, Kreth S, von Deimling A, Tonn JC, Kretzschmar HA, Pöpperl G, Kreth FW (2011b) Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas. Neurooncol 13:307–316Google Scholar
  60. Kwee SA, Ko JP, Jiang CS, Watters MR, Coel MN (2007) Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET. Radiology 244:557–565PubMedCrossRefGoogle Scholar
  61. Langen KJ, Broer S (2004) Molecular transport mechanisms of radiolabeled amino acids for PET and SPECT. J Nucl Med (official publication) 45:1435–1436Google Scholar
  62. Langen KJ, Eschmann SM (2008) Correlative imaging of hypoxia and angiogenesis in oncology. J Nucl Med (official publication) 49:515–516Google Scholar
  63. Langen KJ, Tatsch K, Grosu AL, Jacobs AH, Weckesser M, Sabri O (2008) Diagnostics of cerebral gliomas with radiolabeled amino acids. Dtsch Arztebl Int 105:55–61PubMedPubMedCentralGoogle Scholar
  64. Langen KJ, Jarosch M, Muhlensiepen H, Hamacher K, Broer S, Jansen P, Zilles K, Coenen HH (2003) Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas. Nucl Med Biol 30:501–508PubMedCrossRefGoogle Scholar
  65. 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 33:287–294PubMedCrossRefGoogle Scholar
  66. Lee HY, Chung JK, Jeong JM, Lee DS, Kim DG, Jung HW, Lee MC (2008) Comparison of FDG-PET findings of brain metastasis from non-small-cell lung cancer and small-cell lung cancer. Ann Nucl Med 22:281–286PubMedCrossRefGoogle Scholar
  67. Lee IH, Piert M, Gomez-Hassan D, Junck L, Rogers L, Hayman J, Ten Haken RK, Lawrence TS, Cao Y, Tsien C (2009) Association of 11C-methionine PET uptake with site of failure after concurrent temozolomide and radiation for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys 73:479–485PubMedCrossRefPubMedCentralGoogle Scholar
  68. Lee ST, Scott AM (2007) Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole. Semin Nucl Med 37:451–461PubMedCrossRefGoogle Scholar
  69. Levivier M, Massager N, Wikler D, Lorenzoni J, Ruiz S, Devriendt D, David P, Desmedt F, Simon S, Van Houtte P, Brotchi J, Goldman S (2004) Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification. J Nucl Med (official publication) 45:1146–1154Google Scholar
  70. Lustig RA, Seiferheld W, Berkey B, Yung AW, Scarantino C, Movsas B, Jones CU, Simpson JR, Fishbach J, Curran WJ Jr (2007) Imaging response in malignant glioma, RTOG 90–06. Am J ClinOncol 30:32–37CrossRefGoogle Scholar
  71. Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, Yano H, Iwama T, Hayashi S, Hoshi H, Yamada J, Kanematsu M, Aoyama H (2012) Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys 82:83–89PubMedCrossRefGoogle Scholar
  72. Meller J, Sahlmann CO, Scheel AK (2007) 18F-FDG PET and PET/CT in fever of unknown origin. J Nucl Med (official publication) 48:35–45Google Scholar
  73. Miyake K, Shinomiya A, Okada M, Hatakeyama T, Kawai N, Tamiya T (2012) Usefulness of FDG, MET and FLT-PET studies for the management of human gliomas. J Biomed Biotechnol 2012:205818PubMedCrossRefPubMedCentralGoogle Scholar
  74. Mosskin M, Ericson K, Hindmarsh T, von Holst H, Collins VP, Bergstrom M, Eriksson L, Johnstrom P (1989) Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference. Acta Radiol 30:225–232PubMedCrossRefGoogle Scholar
  75. Narita T, Aoyama H, Hirata K, Onodera S, Shiga T, Kobayashi H, Murata J, Terasaka S, Tanaka S, Houkin K (2012) Reoxygenation of glioblastoma multiforme treated with fractionated radiotherapy concomitant with temozolomide: changes defined by 18F-fluoromisonidazole positron emission tomography: two case reports. Jpn J Clin Oncol 42:120–123PubMedCrossRefGoogle Scholar
  76. Nyuyki F, Plotkin M, Graf R, Michel R, Steffen I, Denecke T, Geworski L, Fahdt D, Brenner W, Wurm R (2010) Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas. Eur J Nucl Med Mol Imaging 37:310–318PubMedCrossRefGoogle Scholar
  77. Padma MV, Said S, Jacobs M, Hwang DR, Dunigan K, Satter M, Christian B, Ruppert J, Bernstein T, Kraus G, Mantil JC (2003) Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol 64:227–237PubMedCrossRefGoogle Scholar
  78. Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Muller HW, Zilles K, Coenen HH, Langen KJ (2005) O–(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain J Neurol 128:678–687CrossRefGoogle Scholar
  79. 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 (18)F-FET and (18)F-FDG PET in brain tumors. Nucl Med Biol 36:779–787PubMedCrossRefGoogle Scholar
  80. 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 37:1521–1528PubMedCrossRefGoogle Scholar
  81. Piroth MD, Pinkawa M, Holy R, Stoffels G, Demirel C, Attieh C, Kaiser HJ, Langen KJ, Eble MJ (2009) Integrated-boost IMRT or 3-D-CRT using FET-PET based auto-contoured target volume delineation for glioblastoma multiforme–a dosimetric comparison. Radiat Oncol 4:57PubMedCrossRefPubMedCentralGoogle Scholar
  82. Piroth MD, Holy R, Pinkawa M, Stoffels G, Kaiser HJ, Galldiks N, Herzog H, Coenen HH, Eble MJ, Langen KJ (2011a) Prognostic impact of postoperative, pre-irradiation (18)F-fluoroethyl-L-tyrosine uptake in glioblastoma patients treated with radiochemotherapy. Radiother Oncol J Eur Soc Ther Radiol Oncol 99:218–224CrossRefGoogle Scholar
  83. Piroth MD, Pinkawa M, Holy R, Klotz J, Nussen S, Stoffels G, Coenen HH, Kaiser HJ, Langen KJ, Eble MJ (2011b) Prognostic value of early [18F]fluoroethyltyrosine positron emission tomography after radiochemotherapy in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 80:176–184PubMedCrossRefGoogle Scholar
  84. Piroth MD, Pinkawa M, Holy R, Klotz J, Schaar S, Stoffels G, Galldiks N, Coenen HH, Kaiser HJ, Langen KJ, Eble MJ (2012) Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. results of a prospective phase II study. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 188:334–339Google Scholar
  85. Pirotte B, Goldman S, Massager N, David P, Wikler D, Lipszyc M, Salmon I, Brotchi J, Levivier M (2004) Combined use of 18Ffluorodeoxyglucose and 11C-methionine in 45 positron emission tomography-guided stereotactic brain biopsies. J Neurosurg 101:476–483PubMedCrossRefGoogle Scholar
  86. Pirotte B, Goldman S, Salzberg S, Wikler D, David P, Vandesteene A, Van Bogaert P, Salmon I, Brotchi J, Levivier M (2003) Combined positron emission tomography and magnetic resonance imaging for the planning of stereotactic brain biopsies in children: experience in 9 cases. Pediatr Neurosurg 38:146–155PubMedCrossRefGoogle Scholar
  87. Pirotte BJ, Lubansu A, Massager N, Wikler D, Goldman S, Levivier M (2007) Results of positron emission tomography guidance and reassessment of the utility of and indications for stereotactic biopsy in children with infiltrative brainstem tumors. J Neurosurg 107:392–399PubMedCrossRefGoogle Scholar
  88. Pirotte BJ, Levivier M, Goldman S, Massager N, Wikler D, Dewitte O, Bruneau M, Rorive S, David P, Brotchi J (2009) Positron emission tomography-guided volumetric resection of supratentorial highgrade gliomas: a survival analysis in 66 consecutive patients. Neurosurgery 64:471–481; discussion 481Google Scholar
  89. Plotkin M, Blechschmidt C, Auf G, Nyuyki F, Geworski L, Denecke T, Brenner W, Stockhammer F (2010) Comparison of F-18 FETPET with F-18 FDG-PET for biopsy planning of non-contrastenhancing gliomas. Eur Radiol 20:2496–2502PubMedCrossRefGoogle Scholar
  90. Pöpperl 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 31:1464–1470PubMedCrossRefGoogle Scholar
  91. Pöpperl G, Gotz C, Rachinger W, Schnell O, Gildehaus FJ, Tonn JC, Tatsch K (2006a) 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 33:792–800PubMedCrossRefPubMedCentralGoogle Scholar
  92. Pöpperl G, Goldbrunner R, Gildehaus FJ, Kreth FW, Tanner P, Holtmannspotter M, Tonn JC, Tatsch K (2005) O–(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convectionenhanced delivery of paclitaxel in patients with recurrent glioblastoma. Eur J Nucl Med Mol Imaging 32:1018–1025PubMedCrossRefGoogle Scholar
  93. Pöpperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, Kretzschmar HA, Tonn JC, Tatsch K (2006b) Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med (official publication) 47:393–403Google Scholar
  94. Pöpperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, Kretzschmar HA, Tonn JC, Tatsch K (2006c) Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med 47:393–403PubMedGoogle Scholar
  95. Pöpperl G, Kreth FW, Mehrkens JH, Herms J, Seelos K, Koch W, Gildehaus FJ, Kretzschmar HA, Tonn JC, Tatsch K (2007) FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. Eur J Nucl Med Mol Imaging 34:1933–1942PubMedCrossRefGoogle Scholar
  96. Prieto E, Marti-Climent JM, Dominguez-Prado I, Garrastachu P, Diez-Valle R, Tejada S, Aristu JJ, Penuelas I, Arbizu J (2011) Voxelbased analysis of dual-time-point 18F-FDG PET images for brain tumor identification and delineation. J Nucl Med (official publication) 52:865–872Google Scholar
  97. Rachinger W, Goetz C, Pöpperl G, Gildehaus FJ, Kreth FW, Holtmannspotter M, Herms J, Koch W, Tatsch K, Tonn JC (2005) Positron emission tomography with O–(2-[18F]fluoroethyl)-L-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery 57:505–511; discussion 505–511Google Scholar
  98. Rapp M, Floeth FW, Felsberg J, Steiger HJ, Sabel M, Langen KJ, Galldiks N (2013a) Clinical value of O–(2-[(18)F]-fluoroethyl)-Ltyrosine positron emission tomography in patients with low-grade glioma. Neurosurg Focus 34:E3PubMedCrossRefGoogle Scholar
  99. 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 (2013b) Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma. J Nucl Med (official publication) 54:229–235Google Scholar
  100. Ribom D, Eriksson A, Hartman M, Engler H, Nilsson A, Langstrom B, Bolander H, Bergstrom M, Smits A (2001) Positron emission tomography (11)C-methionine and survival in patients with lowgrade gliomas. Cancer 92:1541–1549PubMedCrossRefGoogle Scholar
  101. Ricci PE, Karis JP, Heiserman JE, Fram EK, Bice AN, Drayer BP (1998) Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? AJNR Am J Neuroradiol 19:407–413PubMedGoogle Scholar
  102. Rickhey M, Koelbl O, Eilles C, Bogner L (2008) A biologically adapted dose-escalation approach, demonstrated for 18F-FET-PET in brain tumors. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 184:536–542Google Scholar
  103. Roelcke U, Bruehlmeier M, Hefti M, Hundsberger T, Nitzsche EU (2012) F-18 choline PET does not detect increased metabolism in F-18 fluoroethyltyrosine-negative low-grade gliomas. Clin Nucl Med 37:e1–e3PubMedCrossRefGoogle Scholar
  104. Rottenburger C, Hentschel M, Kelly T, Trippel M, Brink I, Reithmeier T, Meyer PT, Nikkhah G (2011) Comparison of C-11 methionine and C-11 choline for PET imaging of brain metastases: a prospective pilot study. Clin Nucl Med 36:639–642PubMedCrossRefGoogle Scholar
  105. Saga T, Kawashima H, Araki N, Takahashi JA, Nakashima Y, Higashi T, Oya N, Mukai T, Hojo M, Hashimoto N, Manabe T, Hiraoka M, Togashi K (2006) Evaluation of primary brain tumors with FLTPET: usefulness and limitations. Clin Nucl Med 31:774–780PubMedCrossRefGoogle Scholar
  106. Salber D, Stoffels G, Pauleit D, Reifenberger G, Sabel M, Shah NJ, Hamacher K, Coenen HH, Langen KJ (2006) Differential uptake of [18F]FET and [3H]L-methionine in focal cortical ischemia. Nucl Med Biol 33:1029–1035PubMedCrossRefGoogle Scholar
  107. Salber D, Stoffels G, Pauleit D, Oros-Peusquens AM, Shah NJ, Klauth P, Hamacher K, Coenen HH, Langen KJ (2007) Differential uptake of O–(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3Hdeoxyglucose in brain abscesses. J Nucl Med (official publication) 48:2056–2062Google Scholar
  108. Saleem A, Brown GD, Brady F, Aboagye EO, Osman S, Luthra SK, Ranicar AS, Brock CS, Stevens MF, Newlands E, Jones T, Price P (2003) Metabolic activation of temozolomide measured in vivo using positron emission tomography. Cancer Res 63:2409–2415PubMedGoogle Scholar
  109. Schiepers C, Dahlbom M, Chen W, Cloughesy T, Czernin J, Phelps ME, Huang SC (2010) Kinetics of 30-deoxy-30-18F-fluorothymidine during treatment monitoring of recurrent high-grade glioma. J Nucl Med (official publication) 51:720–727Google Scholar
  110. Schnell O, Krebs B, Carlsen J, Miederer I, Goetz C, Goldbrunner RH, Wester HJ, Haubner R, Pöpperl G, Holtmannspotter M, Kretzschmar HA, Kessler H, Tonn JC, Schwaiger M, Beer AJ (2009) Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography. Neurooncol 11:861–870Google Scholar
  111. Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Geist C, Dahlbom M, Silverman DH, Satyamurthy N, Phelps ME, Chen W (2012) 30-deoxy-30-18F-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab. J Nucl Med (official publication) 53:29–36Google Scholar
  112. Shields AF (2003) PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med (official publication) 44:1432–1434Google Scholar
  113. Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, Obradovich JE, Muzik O, Mangner TJ (1998) Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 4:1334–1336PubMedCrossRefGoogle Scholar
  114. Singhal T, Narayanan TK, Jain V, Mukherjee J, Mantil J (2008) 11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas. Mol Imaging Biol Official Publ Acad Mol Imaging 10:1–18CrossRefGoogle Scholar
  115. Singhal T, Narayanan TK, Jacobs MP, Bal C, Mantil JC (2012) 11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI. J Nucl Med (official publication) 53:1709–1715Google Scholar
  116. Smits A, Baumert BG (2011) The Clinical Value of PET with Amino Acid Tracers for Gliomas WHO Grade II. Int J Mol Imaging 2011:372509PubMedCrossRefPubMedCentralGoogle Scholar
  117. Smits A, Westerberg E, Ribom D (2008) Adding 11C-methionine PET to the EORTC prognostic factors in grade 2 gliomas. Eur J Nucl Med Mol Imaging 35:65–71PubMedCrossRefGoogle Scholar
  118. Spence AM, Muzi M, Mankoff DA, O’Sullivan SF, Link JM, Lewellen TK, Lewellen B, Pham P, Minoshima S, Swanson K, Krohn KA (2004) 18F-FDG PET of gliomas at delayed intervals: improved distinction between tumor and normal gray matter. J.Nucl Med 45:1653–1659Google Scholar
  119. Tan H, Chen L, Guan Y, Lin X (2011) Comparison of MRI, F-18 FDG, and 11C-choline PET/CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy. Clin Nucl Med 36:978–981PubMedCrossRefGoogle Scholar
  120. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, Ohata K (2008) Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med (official publication) 49:694–699Google Scholar
  121. Thorwarth D, Henke G, Muller AC, Reimold M, Beyer T, Boss A, Kolb A, Pichler B, Pfannenberg C (2011) Simultaneous 68 Ga-DOTATOC-PET/MRI for IMRT treatment planning for meningioma: first experience. Int J Radiat Oncol Biol Phys 81:277–283PubMedCrossRefGoogle Scholar
  122. Tsuyuguchi N, Takami T, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Nishikawa M, Ohata K, Torii K, Morino M, Nishio A, Hara M (2004) Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery—in malignant glioma. Ann Nucl Med 18:291–296PubMedCrossRefGoogle Scholar
  123. Ullrich R, Backes H, Li H, Kracht L, Miletic H, Kesper K, Neumaier B, Heiss WD, Wienhard K, Jacobs AH (2008) Glioma proliferation as assessed by 30-fluoro-30-deoxy-L-thymidine positron emission tomography in patients with newly diagnosed high-grade glioma. Clin Cancer Res Official J Am Assoc Cancer Res 14:2049–2055CrossRefGoogle Scholar
  124. Utriainen M, Metsahonkala L, Salmi TT, Utriainen T, Kalimo H, Pihko H, Makipernaa A, Harila-Saari A, Jyrkkio S, Laine J, Nagren K, Minn H (2002) Metabolic characterization of childhood brain tumors: comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography. Cancer 95:1376–1386PubMedCrossRefGoogle Scholar
  125. Van Laere K, Ceyssens S, Van Calenbergh F, de Groot T, Menten J, Flamen P, Bormans G, Mortelmans L (2005) 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 32:39–51PubMedCrossRefGoogle Scholar
  126. Walter F, Cloughesy T, Walter MA, Lai A, Nghiemphu P, Wagle N, Fueger B, Satyamurthy N, Phelps ME, Czernin J (2012) Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET/CT on managing patients with brain tumors: the referring physician’s perspective. J Nucl Med (official publication) 53:393–398CrossRefGoogle Scholar
  127. Weber DC, Casanova N, Zilli T, Buchegger F, Rouzaud M, Nouet P, Vees H, Ratib O, Dipasquale G, Miralbell R (2009) Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study. Radiother Oncol J Eur Soc Ther Radiol Oncol 93:586–592CrossRefGoogle Scholar
  128. Weber DC, Zilli T, Buchegger F, Casanova N, Haller G, Rouzaud M, Nouet P, Dipasquale G, Ratib O, Zaidi H, Vees H, Miralbell R (2008) [(18)F]Fluoroethyltyrosine- positron emission tomographyguided radiotherapy for high-grade glioma. Radiat Oncol 3:44Google Scholar
  129. Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, Molls M, Stocklin G, Schwaiger M (2000) 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 27:542–549PubMedCrossRefGoogle Scholar
  130. Weckesser M, Matheja P, Rickert CH, Strater R, Palkovic S, Lottgen J, Kurlemann G, Paulus W, Wassmann H, Schober O (2001) High uptake of L-3-[123I]iodo-alpha-methyl tyrosine in pilocytic astrocytomas. Eur J Nucl Med 28:273–281PubMedCrossRefGoogle Scholar
  131. 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 32:422–429PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Institute of Neuroscience and MedicineForschungszentrum JülichJülichGermany
  2. 2.Department of Nuclear MedicineRWTH Aachen University HospitalAachenGermany
  3. 3.Department of NeurologyUniversity of CologneCologneGermany

Personalised recommendations