Skip to main content

Repeated amino acid PET imaging for longitudinal monitoring of brain tumors

Abstract

Purpose

Amino acid PET is a useful complement to MRI in a number of clinical settings for the evaluation of brain tumors. However, amino acid PET is rarely used repeatedly over the course of the disease. We reviewed the existing literature on the use of repeated amino acid PET imaging for monitoring primary or secondary brain tumors.

Methods

A comprehensive literature search of articles describing the use of longitudinal amino acid PET imaging of brain tumors was performed on PubMed/MEDLINE using multiple search terms. Additional literature was retrieved from the reference lists of identified studies or based on the authors’ personal knowledge and experience.

Results

With regard to primary tumors, two main clinical settings were identified in whom the performance of repeated amino acid PET imaging was most commonly assessed. These include the detection of malignant progression of patients with grade II or III glioma characterized according to older WHO classifications, and the early response assessment of various treatment options in glioma patients. For patients with brain metastases, only a few studies were identified using longitudinal amino acid PET for the diagnosis of post-treatment changes after stereotactic radiosurgery. The analyzed studies reported that longitudinal amino acid PET imaging frequently anticipate or even outperform the diagnostic performance provided by conventional MRI in these settings.

Conclusions

The available literature suggests that conventional MRI should be accompanied by longitudinal amino acid PET monitoring in these clinical settings. Nevertheless, more reliable evidence derived from larger, prospective multicenter studies is warranted.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Langen KJ, Galldiks N, Hattingen E, Shah NJ (2017) Advances in neuro-oncology imaging. Nat Rev Neurol 13:279–289

    PubMed  Article  Google Scholar 

  2. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    PubMed  Article  Google Scholar 

  3. van den Bent MJ, Wefel JS, Schiff D, Taphoorn MJ, Jaeckle K, Junck L, Armstrong T, Choucair A, Waldman AD, Gorlia T, Chamberlain M, Baumert BG, Vogelbaum MA, Macdonald DR, Reardon DA, Wen PY, Chang SM, Jacobs AH (2011) Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol 12:583–593

    PubMed  Article  Google Scholar 

  4. Castellano A, Bailo M, Cicone F, Carideo L, Quartuccio N, Mortini P, Falini A, Cascini GL, Minniti G (2021) Advanced imaging techniques for radiotherapy planning of gliomas. Cancers (Basel) 13:1063

    CAS  Article  Google Scholar 

  5. Filss CP, Cicone F, Shah NJ, Galldiks N, Langen KJ (2017) Amino acid PET and MR perfusion imaging in brain tumours. Clin Transl Imaging 5:209–223

    PubMed  Article  PubMed Central  Google Scholar 

  6. Galldiks N, Albert NL, Sommerauer M, Grosu AL, Ganswindt U, Law I, Preusser M, Le Rhun E, Vogelbaum MA, Zadeh G, Dhermain F, Weller M, Langen KJ, Tonn JC (2017) PET imaging in patients with meningioma-report of the RANO/PET Group. Neuro Oncol 19:1576–1587

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. Galldiks N, Langen KJ, Albert NL, Chamberlain M, Soffietti R, Kim MM, Law I, Le Rhun E, Chang S, Schwarting J, Combs SE, Preusser M, Forsyth P, Pope W, Weller M, Tonn JC (2019) PET imaging in patients with brain metastasis-report of the RANO/PET group. Neuro Oncol 21:585–595

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  8. Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, la Fougère C, Pope W, Law I, Arbizu J, Chamberlain MC, Vogelbaum M, Ellingson BM, Tonn JC (2016) 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 18:1199–1208

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. Galldiks N, Niyazi M, Grosu AL, Kocher M, Langen KJ, Law I, Minniti G, Kim MM, Tsien C, Dhermain F, Soffietti R, Mehta MP, Weller M, Tonn JC (2021) Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group. Neuro Oncol 23:881–893

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. Herrmann K, Czernin J, Cloughesy T, Lai A, Pomykala KL, Benz MR, Buck AK, Phelps ME, Chen W (2014) Comparison of visual and semiquantitative analysis of 18F-FDOPA-PET/CT for recurrence detection in glioblastoma patients. Neuro Oncol 16:603–609

    PubMed  Article  Google Scholar 

  11. Galldiks N, Stoffels G, Filss C, Rapp M, Blau T, Tscherpel C, Ceccon G, Dunkl V, Weinzierl M, Stoffel M, Sabel M, Fink GR, Shah NJ, Langen KJ (2015) The use of dynamic O-(2–18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro Oncol 17:1293–1300

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. Cicone F, Minniti G, Romano A, Papa A, Scaringi C, Tavanti F, Bozzao A, Maurizi Enrici R, Scopinaro F (2015) Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery. Eur J Nucl Med Mol Imaging 42:103–111

    CAS  PubMed  Article  Google Scholar 

  13. Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, Bauer E, Hamisch C, Ruge MI, Kocher M, Kuchelmeister K, Sellhaus B, Sabel M, Fink GR, Shah NJ, Langen KJ, Galldiks N (2017) Dynamic O-(2–18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol 19:281–288

    CAS  PubMed  Google Scholar 

  14. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    PubMed  Article  PubMed Central  Google Scholar 

  15. Soffietti R, Baumert BG, Bello L, Von Deimling A, Duffau H, Frénay M, Grisold W, Grant R, Graus F, Hoang-Xuan K, Klein M, Melin B, Rees J, Siegal T, Smits A, Stupp R, Wick W (2010) Guidelines on management of low-grade gliomas: report of an EFNS-EANO task force. Eur J Neurol 17:1124–1133

    CAS  PubMed  Article  Google Scholar 

  16. Jakola AS, Myrmel KS, Kloster R, Torp SH, Lindal S, Unsgård G, Solheim O (2012) Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA 308:1881–1888

    CAS  PubMed  Article  Google Scholar 

  17. Scott JN, Brasher PM, Sevick RJ, Rewcastle NB, Forsyth PA (2002) How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology 59:947–949

    CAS  PubMed  Article  Google Scholar 

  18. Ullrich RT, Kracht L, Brunn A, Herholz K, Frommolt P, Miletic H, Deckert M, Heiss WD, Jacobs AH (2009) Methyl-L-11C-methionine PET as a diagnostic marker for malignant progression in patients with glioma. J Nucl Med 50:1962–1968

    PubMed  Article  Google Scholar 

  19. Galldiks N, Stoffels G, Ruge MI, Rapp M, Sabel M, Reifenberger G, Erdem Z, Shah NJ, Fink GR, Coenen HH, Langen KJ (2013) 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 54:2046–54.

  20. Unterrainer M, Schweisthal F, Suchorska B, Wenter V, Schmid-Tannwald C, Fendler WP, Schüller U, Bartenstein P, Tonn JC, Albert NL (2016) Serial 18F-FET PET imaging of primarily 18F-FET-negative glioma: does it make sense? J Nucl Med 57:1177–1182

    CAS  PubMed  Article  Google Scholar 

  21. Oughourlian TC, Yao J, Schlossman J, Raymond C, Ji M, Tatekawa H, Salamon N, Pope WB, Czernin J, Nghiemphu PL, Lai A, Cloughesy TF, Ellingson BM (2020) Rate of change in maximum 18F-FDOPA PET uptake and non-enhancing tumor volume predict malignant transformation and overall survival in low-grade gliomas. J Neurooncol 147:135–145

    PubMed  Article  PubMed Central  Google Scholar 

  22. Voges J, Herholz K, Hölzer T, Würker M, Bauer B, Pietrzyk U, Treuer H, Schröder R, Sturm V, Heiss WD (1997) 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 69:129–135

    CAS  PubMed  Article  Google Scholar 

  23. Nuutinen J, Sonninen P, Lehikoinen P, Sutinen E, Valavaara R, Eronen E, Norrgård S, Kulmala J, Teräs M, Minn H (2000) 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 48:43–52

    CAS  PubMed  Article  Google Scholar 

  24. Ribom D, Schoenmaekers M, Engler H, Smits A (2005) Evaluation of 11C-methionine PET as a surrogate endpoint after treatment of grade 2 gliomas J Neurooncol 71:325–32.

  25. Tang BN, Sadeghi N, Branle F, De Witte O, Wikler D, Goldman S (2005) Semi-quantification of methionine uptake and flair signal for the evaluation of chemotherapy in low-grade oligodendroglioma. J Neurooncol 71:161–168

    CAS  PubMed  Article  Google Scholar 

  26. Wyss M, Hofer S, Bruehlmeier M, Hefti M, Uhlmann C, Bärtschi E, Buettner UW, Roelcke U (2009) Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol 95:87–93

    CAS  PubMed  Article  Google Scholar 

  27. Roelcke U, Wyss MT, Nowosielski M, Rudà R, Roth P, Hofer S, Galldiks N, Crippa F, Weller M, Soffietti R (2016) Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas. Neuro Oncol 18:744–751

    CAS  PubMed  Article  Google Scholar 

  28. Suchorska B, Unterrainer M, Biczok A, Sosnova M, Forbrig R, Bartenstein P, Tonn JC, Albert NL, Kreth FW (2018) 18F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy. J Neurooncol 139:721–730

    CAS  PubMed  Article  Google Scholar 

  29. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  Google Scholar 

  30. Langen KJ, Heinzel A, Lohmann P, Mottaghy FM, Galldiks N (2020) Advantages and limitations of amino acid PET for tracking therapy response in glioma patients. Expert Rev Neurother 20:137–146

    CAS  PubMed  Article  Google Scholar 

  31. Prather KY, O'Neal CM, Westrup AM, Tullos HJ, Hughes KL, Conner AK, Glenn CA, Battiste JD (2022) A systematic review of amino acid PET in assessing treatment response to temozolomide in glioma. Neurooncol Adv 4:vdac008.

  32. Galldiks N, Langen KJ, Holy R, Pinkawa M, Stoffels G, Nolte KW, Kaiser HJ, Filss CP, Fink GR, Coenen HH, Eble MJ, Piroth MD (2012) Assessment of treatment response in patients with glioblastoma using O-(2–18F-fluoroethyl)-L-tyrosine PET in comparison to MRI. J Nucl Med 53:1048–1057

    CAS  PubMed  Article  Google Scholar 

  33. Suchorska B, Jansen NL, Linn J, Kretzschmar H, Janssen H, Eigenbrod S, Simon M, Pöpperl G, Kreth FW, la Fougere C, Weller M, Tonn JC, Network GG (2015) Biological tumor volume in 18FET-PET before radiochemotherapy correlates with survival in GBM. Neurology 84:710–719

    CAS  PubMed  Article  Google Scholar 

  34. Piroth MD, Liebenstund S, Galldiks N, Stoffels G, Shah NJ, Eble MJ, Coenen HH, Langen KJ (2013) Monitoring of radiochemotherapy in patients with glioblastoma using O-(2-[18F]Fluoroethyl)-L-tyrosine positron emission tomography: is dynamic imaging helpful? Mol Imaging 12:388–395

    CAS  PubMed  Article  Google Scholar 

  35. Kawasaki T, Miwa K, Shinoda J, Asano Y, Takei H, Ikegame Y, Yokoyama K, Yano H, Iwama T (2019) Dissociation between 11C-methionine-positron emission tomography and gadolinium-enhanced magnetic resonance imaging in longitudinal features of glioblastoma after postoperative radiotherapy. World Neurosurg 125:93–100

    PubMed  Article  Google Scholar 

  36. 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 33:516–524

    CAS  PubMed  Article  Google Scholar 

  37. Ceccon G, Lohmann P, Werner JM, Tscherpel C, Dunkl V, Stoffels G, Rosen J, Rapp M, Sabel M, Herrlinger U, Schäfer N, Shah NJ, Fink GR, Langen KJ, Galldiks N (2021) Early treatment response assessment using 18F-FET PET compared with contrast-enhanced MRI in glioma patients after adjuvant temozolomide chemotherapy. J Nucl Med 62:918–925

    CAS  PubMed  Article  Google Scholar 

  38. 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 52:856–864

    CAS  PubMed  Article  Google 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. Neuro Oncol 14:1079–1089

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 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-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging 40:22–33

    CAS  PubMed  Article  Google Scholar 

  41. Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Grogan T, Elashoff D, Geist C, Silverman DH, Phelps ME, Chen W (2014) Treatment response evaluation using 18F-FDOPA PET in patients with recurrent malignant glioma on bevacizumab therapy. Clin Cancer Res 20:3550–3559

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. Jansen NL, Suchorska B, Schwarz SB, Eigenbrod S, Lutz J, Graute V, Bartenstein P, Belka C, Kreth FW, la Fougère C (2013) [18F]fluoroethyltyrosine-positron emission tomography-based therapy monitoring after stereotactic iodine-125 brachytherapy in patients with recurrent high-grade glioma. Mol Imaging 12:137–147

    CAS  PubMed  Article  Google Scholar 

  43. Stockham AL, Tievsky AL, Koyfman SA, Reddy CA, Suh JH, Vogelbaum MA, Barnett GH, Chao ST (2012) Conventional MRI does not reliably distinguish radiation necrosis from tumor recurrence after stereotactic radiosurgery. J Neurooncol 109:149–158

    PubMed  Article  Google Scholar 

  44. Cicone F, Carideo L, Scaringi C, Romano A, Mamede M, Papa A, Tofani A, Cascini GL, Bozzao A, Scopinaro F, Minniti G (2021) Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET. Neuro Oncol 23:1024–1034

    CAS  PubMed  Article  Google Scholar 

  45. Galldiks N, Stoffels G, Werner J, Bauer EK, Baues C, Celik E, Ruge MI, Fink GR, Langen KJ, Lohmann P (2021) Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging. Neuro Oncol 23(Supp_2):ii6. https://doi.org/10.1093/neuonc/noab180.016

  46. Galldiks N, Abdulla DSY, Scheffler M, Wolpert F, Werner JM, Hüllner M, Stoffels G, Schweinsberg V, Schlaak M, Kreuzberg N, Landsberg J, Lohmann P, Ceccon G, Baues C, Trommer M, Celik E, Ruge MI, Kocher M, Marnitz S, Fink GR, Tonn JC, Weller M, Langen KJ, Wolf J, Mauch C (2021) Treatment monitoring of immunotherapy and targeted therapy using 18F-FET PET in patients with melanoma and lung cancer brain metastases: initial experiences. J Nucl Med 62:464–470

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. Carideo L, Minniti G, Mamede M, Scaringi C, Russo I, Scopinaro F, Cicone F (2018) 18F-DOPA uptake parameters in glioma: effects of patients’ characteristics and prior treatment history. Br J Radiol 91:20170847

    PubMed  Article  PubMed Central  Google Scholar 

  48. Stegmayr C, Stoffels G, Kops ER, Lohmann P, Galldiks N, Shah NJ, Neumaier B, Langen KJ (2019) Influence of dexamethasone on O-(2-[18F]-fluoroethyl)-L-tyrosine uptake in the human brain and quantification of tumor uptake. Mol Imaging Biol 21:168–174

    CAS  PubMed  Article  Google Scholar 

  49. Hutterer M, Bumes E, Riemenschneider MJ, Grosse J, Hellwig D, Galldiks N, Langen KJ, Hau P (2017) AIDS-related central nervous system toxoplasmosis with increased 18F-fluoroethyl-L-tyrosine amino acid PET uptake due to LAT1/2 expression of inflammatory cells. Clin Nucl Med 42:e506–e508

    PubMed  Article  Google Scholar 

  50. Cicone F, Carideo L, Villani V, Scaringi C, Bozzao A, Scopinaro F, Minniti G (2020) Metabolic evolution of brain metastasis after stereotactic radiosurgery: mismatch between F-DOPA and FDG PET. Clin Nucl Med 45:557–558

    PubMed  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conception and design of the article: FC. Literature search, drafting of the article: FC, NG, AP, KJL, GLC, GM. Final approval of the version to be published: FC, NG, AP, KJL, GLC, GM.

Corresponding author

Correspondence to Francesco Cicone.

Ethics declarations

Conflict of interest

Francesco Cicone, Norbert Galldiks, Annalisa Papa, Karl-Josef Langen, Giuseppe Lucio Cascini, and Giuseppe Minniti have no relevant financial or non-financial interests to disclose.

Human studies

This article does not contain any studies with human or animal subjects performed by the any of the authors.

Ethical approval and Informed consent

The article is a literature review for which no ethical approval or consent to participate is required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cicone, F., Galldiks, N., Papa, A. et al. Repeated amino acid PET imaging for longitudinal monitoring of brain tumors. Clin Transl Imaging (2022). https://doi.org/10.1007/s40336-022-00504-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40336-022-00504-w

Keywords

  • Amino acid PET
  • Glioma
  • Brain metastases
  • Response assessment
  • Longitudinal imaging
  • Follow-up