The Use of PET/CT in Radiotherapy Planning for Brain Tumours

  • Francesca SoldáEmail author
  • Naomi Fersht
Part of the Clinicians’ Guides to Radionuclide Hybrid Imaging book series (CGRHI)


Accurate identification of the treatment target is of crucial importance in modern brain radiotherapy, where the implementation of high-precision techniques of irradiation (intensity-modulated radiotherapy (IMRT), stereotactic radiotherapy (SRT) and stereotactic radiosurgery (SRS)) and the use of image guidance (IGRT) allow maximisation of the dose to the tumour volume identified while simultaneously sparing the surrounding uninvolved healthy brain [1].


  1. 1.
    Khuntia D, Tomé WA, Mehta MP. Radiation techniques in neuro-oncology. Neurotherapeutics. 2009;6:487–99.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Burnet NG, Thomas SJ, Burton KE, Jefferies SJ. Defining the tumour and target volumes for radiotherapy. Cancer Imaging. 2004;4:153–61.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Niyazi M, Brada M, Chalmers AJ, Combs SE, Erridge SC, Fiorentino A, et al. ESTRO-ACROP guideline “target delineation of glioblastomas”. Radiother Oncol. 2016;118:35–42.PubMedGoogle Scholar
  4. 4.
    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;18:1199–208.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Jaeckle KA. Neuroimaging for central nervous system tumors. Semin Oncol. 1991;18:150–7.PubMedGoogle Scholar
  6. 6.
    la Fougère C, Suchorska B, Bartenstein P, Kreth F-W, Tonn J-C. Molecular imaging of gliomas with PET: opportunities and limitations. Neuro Oncol. 2011;13:806–19.PubMedPubMedCentralGoogle Scholar
  7. 7.
    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;19:407–13.PubMedGoogle Scholar
  8. 8.
    Wong TZ, van der Westhuizen GJ, Coleman RE. Positron emission tomography imaging of brain tumors. Neuroimaging Clin N Am. 2002;12:615–26.PubMedGoogle Scholar
  9. 9.
    Di Chiro G, Hatazawa J, Katz DA, Rizzoli HV, De Michele DJ. Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study. Radiology. 1987;164:521–6.PubMedGoogle Scholar
  10. 10.
    Valotassiou V, Leondi A, Angelidis G, Psimadas D, Georgoulias P. SPECT and PET imaging of meningiomas. ScientificWorldJournal. 2012;2012:412580.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kumar R, Chauhan A, Zhuang H, Chandra P, Schnall M, Alavi A. Clinicopathologic factors associated with false negative FDG-PET in primary breast cancer. Breast Cancer Res Treat. 2006;98:267–74.PubMedGoogle Scholar
  12. 12.
    Jeraj R, Bradshaw T, Simoncic U. Molecular imaging to plan radiotherapy and evaluate its efficacy. J Nucl Med. 2015;56:1752–65.PubMedGoogle Scholar
  13. 13.
    Kristiansen K, Hagen S, Kollevold T, Torvik A, Holme I, Nesbakken R, et al. Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer. 1981;47:649–52.PubMedGoogle Scholar
  14. 14.
    Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49:333–43.Google Scholar
  15. 15.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.Google Scholar
  16. 16.
    Niyazi M, Siefert A, Schwarz SB, Ganswindt U, Kreth FW, Tonn JC, et al. Therapeutic options for recurrent malignant glioma. Radiother Oncol. 2011;98:1–14.PubMedGoogle Scholar
  17. 17.
    Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, et al. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:64–74.PubMedGoogle Scholar
  18. 18.
    Susheela S, Revannasiddaiah S, Madhusudhan N, Bijjawara M. The demonstration of extension of high-grade glioma beyond magnetic resonance imaging defined edema by the use of 11C-methionine positron emission tomography. J Cancer Res Ther. 2013;9:715–7.PubMedGoogle Scholar
  19. 19.
    Zetterling M, Roodakker KR, Berntsson SG, Edqvist PH, Latini F, Landtblom AM, et al. Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data. J Neurosurg. 2016;125:1155–66.PubMedGoogle Scholar
  20. 20.
    Lee SW, Fraass BA, Marsh LH, Herbort K, Gebarski SS, Martel MK, et al. Patterns of failure following high-dose 3-D conformal radiotherapy for high-grade astrocytomas: a quantitative dosimetric study. Int J Radiat Oncol Biol Phys. 1999;43:79–88.PubMedGoogle Scholar
  21. 21.
    Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990;8:1277–80.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Giantsoudi D, Adams J, MacDonald SM, Paganetti H. Proton treatment techniques for posterior fossa tumors: consequences for linear energy transfer and dose-volume parameters for the brainstem and organs at risk. Int J Radiat Oncol Biol Phys. 2017;97:401–10.PubMedGoogle Scholar
  23. 23.
    Oppitz U, Maessen D, Zunterer H, Richter S, Flentje M. 3D-recurrence-patterns of gliobastomas after CT-planned postoperative irradiation. Radiother Oncol. 1999;53:53–7.PubMedGoogle Scholar
  24. 24.
    Niyazi M, Geisler J, Siefert A, Schwarz SB, Ganswindt U, Garny S, et al. FET-PET for malignant glioma treatment planning. Radiother Oncol. 2011;99:44–8.PubMedGoogle Scholar
  25. 25.
    Lee IH, Piert M, Gomez-Hassan D, Junck L, Rogers L, Hayman J, et al. 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. 2009;73:479–85.PubMedGoogle Scholar
  26. 26.
    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.PubMedPubMedCentralGoogle Scholar
  27. 27.
    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;63:511–9.PubMedGoogle Scholar
  28. 28.
    Nuutinen J, Sonninen P, Lehikoinen P, Sutinen E, Valavaara R, Eronen E, et al. Radiotherapy treatment planning and long-term follow-up with [11C]methionine PET in patients with low-grade astrocytoma. Int J Radiat Oncol Biol Phys. 2000;48:43–52.PubMedGoogle Scholar
  29. 29.
    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;109:487–92.PubMedGoogle Scholar
  30. 30.
    Fueger BJ, Czernin J, Cloughesy T, Silverman DH, Geist CL, Walter MA, et al. Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas. J Nucl Med. 2010;51:1532–8.PubMedGoogle Scholar
  31. 31.
    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;10:7163–70.PubMedGoogle Scholar
  32. 32.
    Tripathi M, Sharma R, D’Souza M, Jaimini A, Panwar P, Varshney R, et al. Comparative evaluation of F-18 FDOPA, F-18 FDG, and F-18 FLT-PET/CT for metabolic imaging of low grade gliomas. Clin Nucl Med. 2009;34:878–83.PubMedGoogle Scholar
  33. 33.
    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;128:678–87.Google Scholar
  34. 34.
    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.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Vees H, Senthamizhchelvan S, Miralbell R, Weber DC, Ratib O, Zaidi H. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients. Eur J Nucl Med Mol Imaging. 2009;36:182–93.PubMedGoogle Scholar
  36. 36.
    Schinkelshoek M, Lopci E, Clerici E, Alongi F, Mancosu P, Rodari M, et al. Impact of 11C-methionine positron emission tomography/computed tomography on radiation therapy planning and prognosis in patients with primary brain tumors. Tumori. 2014;100:636–44.PubMedGoogle Scholar
  37. 37.
    Munck af Rosenschold P, Costa J, Engelholm SA, Lundemann MJ, Law I, Ohlhues L, et al. Impact of [(18)F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma. Neuro Oncol. 2015;17:757–63.PubMedGoogle Scholar
  38. 38.
    Moller S, Law I, Munck af Rosenschold P, Costa J, Poulsen HS, Engelholm SA, et al. Prognostic value of 18F-FET PET imaging in re-irradiation of high-grade glioma: results of a phase I clinical trial. Radiother Oncol. 2016;121:132–7.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Poulsen SH, Urup T, Grunnet K, Christensen IJ, Larsen VA, Jensen ML, et al. The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma. Eur J Nucl Med Mol Imaging. 2017;44:373–81.PubMedGoogle Scholar
  40. 40.
    Jaymanne DT, Kaushal S, Chan D, Schembri G, Brazier D, Bailey D, et al. Utilizing 18F-fluoroethyl-l-tyrosine positron emission tomography in high grade glioma for radiation treatment planning in patients with contraindications to MRI. J Med Imaging Radiat Oncol. 2018;62:122–7.PubMedGoogle Scholar
  41. 41.
    Mahasittiwat P, Mizoe JE, Hasegawa A, Ishikawa H, Yoshikawa K, Mizuno H, et al. l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70:515–22.PubMedGoogle Scholar
  42. 42.
    Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, et al. Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys. 2012;82:83–9.PubMedGoogle Scholar
  43. 43.
    Miwa K, Matsuo M, Ogawa S-I, Shinoda J, Yokoyama K, Yamada J, et al. Re-irradiation of recurrent glioblastoma multiforme using (11)C-methionine PET/CT/MRI image fusion for hypofractionated stereotactic radiotherapy by intensity modulated radiation therapy. Radiat Oncol. 2014;9:181.PubMedPubMedCentralGoogle Scholar
  44. 44.
    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;87:1100–6.PubMedGoogle Scholar
  45. 45.
    Combs SE, Ganswindt U, Foote RL, Kondziolka D, Tonn JC. State-of-the-art treatment alternatives for base of skull meningiomas: complementing and controversial indications for neurosurgery, stereotactic and robotic based radiosurgery or modern fractionated radiation techniques. Radiat Oncol. 2012;7:226.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Lee JW, Kang KW, Park SH, Lee SM, Paeng JC, Chung JK, et al. 18F-FDG PET in the assessment of tumor grade and prediction of tumor recurrence in intracranial meningioma. Eur J Nucl Med Mol Imaging. 2009;36:1574–82.PubMedGoogle Scholar
  47. 47.
    Liu RS, Chang CP, Guo WY, Pan DH, Ho DM, Chang CW, et al. 1-11C-acetate versus 18F-FDG PET in detection of meningioma and monitoring the effect of gamma-knife radiosurgery. J Nucl Med. 2010;51:883–91.PubMedGoogle Scholar
  48. 48.
    Dutour A, Kumar U, Panetta R, Ouafik L, Fina F, Sasi R, et al. Expression of somatostatin receptor subtypes in human brain tumors. Int J Cancer. 1998;76:620–7.PubMedGoogle Scholar
  49. 49.
    Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J, et al. PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med. 2001;42:1053–6.PubMedGoogle Scholar
  50. 50.
    d’Amico A, Stapor-Fudzinska M, Tarnawski R. CyberKnife radiosurgery planning of a secreting pituitary adenoma performed with (6)(8)Ga DOTATATE PET and MRI. Clin Nucl Med. 2014;39:1043–4.PubMedGoogle Scholar
  51. 51.
    Astner ST, Bundschuh RA, Beer AJ, Ziegler SI, Krause BJ, Schwaiger M, et al. Assessment of tumor volumes in skull base glomus tumors using Gluc-Lys[(18)F]-TOCA positron emission tomography. Int J Radiat Oncol Biol Phys. 2009;73:1135–40.PubMedGoogle Scholar
  52. 52.
    Milker-Zabel S, Zabel-du Bois A, Henze M, Huber P, Schulz-Ertner D, Hoess A, et al. Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys. 2006;65:222–7.PubMedGoogle Scholar
  53. 53.
    Gehler B, Paulsen F, Öksüz MÖ, Hauser T-K, Eschmann SM, Bares R, et al. [(68)Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning. Radiat Oncol. 2009;4:56.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Nyuyki F, Plotkin M, Graf R, Michel R, Steffen I, Denecke T, et al. Potential impact of 68Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas. Eur J Nucl Med Mol Imaging. 2010;37:310–8.PubMedGoogle Scholar
  55. 55.
    Combs SE, Welzel T, Habermehl D, Rieken S, Dittmar J-O, Kessel K, et al. Prospective evaluation of early treatment outcome in patients with meningiomas treated with particle therapy based on target volume definition with MRI and 68Ga-DOTATOC-PET. Acta Oncol. 2013;52:514–20.PubMedGoogle Scholar
  56. 56.
    Graf R, Nyuyki F, Steffen IG, Michel R, Fahdt D, Wust P, et al. Contribution of 68Ga-DOTATOC PET/CT to target volume delineation of skull base meningiomas treated with stereotactic radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:68–73.PubMedGoogle Scholar
  57. 57.
    Maclean J, Fersht N, Sullivan K, Kayani I, Bomanji J, Dickson J, et al. Simultaneous (68)Ga DOTATATE positron emission tomography/magnetic resonance imaging in meningioma target contouring: feasibility and impact upon interobserver variability versus positron emission tomography/computed tomography and computed tomography/magnetic resonance imaging. Clin Oncol. 2017;29:448–58.Google Scholar
  58. 58.
    Grosu A-L, Weber WA, Astner ST, Adam M, Krause BJ, Schwaiger M, et al. 11C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2006;66:339–44.PubMedGoogle Scholar
  59. 59.
    Astner ST, Dobrei-Ciuchendea M, Essler M, Bundschuh RA, Sai H, Schwaiger M, et al. Effect of 11C-methionine-positron emission tomography on gross tumor volume delineation in stereotactic radiotherapy of skull base meningiomas. Int J Radiat Oncol Biol Phys. 2008;72:1161–7.PubMedGoogle Scholar
  60. 60.
    Glaudemans AW, Enting RH, Heesters MA, Dierckx RA, van Rheenen RW, Walenkamp AM, et al. Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging. 2013;40:615–35.PubMedGoogle Scholar
  61. 61.
    Stober B, Tanase U, Herz M, Seidl C, Schwaiger M, Senekowitsch-Schmidtke R. Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells. Eur J Nucl Med Mol Imaging. 2006;33:932–9.PubMedGoogle Scholar
  62. 62.
    Miwa K, Matsuo M, Shinoda J, Aki T, Yonezawa S, Ito T, et al. Clinical value of [(1)(1)C]methionine PET for stereotactic radiation therapy with intensity modulated radiation therapy to metastatic brain tumors. Int J Radiat Oncol Biol Phys. 2012;84:1139–44.PubMedGoogle Scholar
  63. 63.
    Matsuo M, Miwa K, Shinoda J, Kako N, Nishibori H, Sakurai K, et al. Target definition by C11-methionine-PET for the radiotherapy of brain metastases. Int J Radiat Oncol Biol Phys. 2009;74:714–22.PubMedGoogle Scholar
  64. 64.
    Götz I, Grosu AL. [(18)F]FET-PET imaging for treatment and response monitoring of radiation therapy in malignant glioma patients – a review. Front Oncol. 2013;3:104.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Galldiks N, Albert NL, Sommerauer M, Grosu AL, Ganswindt U, Law I, et al. PET imaging in patients with meningioma-report of the RANO/PET Group. Neuro Oncol. 2017;19:1576–87.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of OncologyUniversity College HospitalLondonUK

Personalised recommendations