Abstract
Purpose
For the clinical evaluation of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET images, the use of standard summation images obtained 20–40 min after injection is recommended. However, early summation images obtained 5–15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification.
Methods
The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5–15 min and standard 20–40 min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status).
Results
In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53).
Conclusion
BTVs delineated in early and standard summation images differed significantly in more than half of gliomas. While the standard summation images seem appropriate for delineation of LGG as well as IDH-mutant gliomas, a remarkably high percentage of HGG and, particularly, IDH-wildtype gliomas were depicted with significantly larger volumes in early summation images. This finding might be of interest for optimization of treatment planning (e.g. radiotherapy) in accordance with the individual IDH mutation status.
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Change history
15 March 2018
The name of M. Unterrainer was inadvertently presented as M. Unterrrainer in the original article.
References
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.
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.
Jansen NL, Suchorska B, Wenter V, Eigenbrod S, Schmid-Tannwald C, Zwergal A, et al. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients. J Nucl Med. 2014;55(2):198–203.
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.
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 gGlioma: does it make sense? J Nucl Med. 2016;57(8):1177–82.
Pirotte BJ, Levivier M, Goldman S, Massager N, Wikler D, Dewitte O, et al. Positron emission tomography-guided volumetric resection of supratentorial high-grade gliomas: a survival analysis in 66 consecutive patients. Neurosurgery. 2009;64(3):471–81.
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(1):44–8.
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.
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. 2011;50:167–73.
Vander Borght T, Asenbaum S, Bartenstein P, Halldin C, Kapucu Ö, 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.
Albert NL, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E, et al. Early static (18)F-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.
Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20.
Weller M, Pfister SM, Wick W, Hegi ME, Reifenberger G, Stupp R. Molecular neuro-oncology in clinical practice: a new horizon. Lancet Oncol. 2013;14(9):e370–e9.
Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129(4):585–96.
Yang P, Cai J, Yan W, Zhang W, Wang Y, Chen B, et al. Classification based on mutations of TERT promoter and IDH characterizes subtypes in grade II/III gliomas. Neuro-Oncology. 2016;18(8):1099–108.
Unterrainer M, Vettermann F, Brendel M, Holzgreve A, Lifschitz M, Zähringer M, et al. Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment? EJNMMI Res. 2017;7(1):48.
Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Muller HW, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128(Pt 3):678–87.
Wyss M, Hofer S, Bruehlmeier M, Hefti M, Uhlmann C, Bärtschi E, et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol. 2009;95(1):87–93.
Galldiks N, Langen K-J, Holy R, Pinkawa M, Stoffels G, Nolte KW, et al. Assessment of treatment response in patients with glioblastoma using O-(2-18F-fluoroethyl)-l-tyrosine PET in comparison to MRI. J Nucl Med. 2012;53(7):1048–57.
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.
Thon N, Eigenbrod S, Kreth S, Lutz J, Tonn JC, Kretzschmar H, et al. IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival. Cancer. 2012;118(2):452–60.
Thon N, Eigenbrod S, Grasbon-Frodl EM, Ruiter M, Mehrkens JH, Kreth S, et al. Novel molecular stereotactic biopsy procedures reveal intratumoral homogeneity of loss of heterozygosity of 1p/19q and TP53 mutations in World Health Organization grade II gliomas. J Neuropathol Exp Neurol. 2009;68(11):1219–28.
Suchorska B, Giese A, Biczok A, Unterrainer M, Weller M, Drexler M, et al. Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma. Neuro Oncol. 2018;20(2):279–88.
Lohmann P, Herzog H, Rota Kops E, Stoffels G, Judov N, Filss C, et al. Dual-time-point O-(2-[18F]fluoroethyl)-L-tyrosine PET for grading of cerebral gliomas. Eur Radiol. 2015;25(10):3017–24.
Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM. Selective expression of the large neutral amino acid transporter at the blood–brain barrier. Proc Natl Acad Sci U S A. 1999;96(21):12079–84.
Habermeier A, Graf J, Sandhöfer B, Boissel J-P, Roesch F, Closs EI. System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. 2015;47(2):335–44.
Harat M, Małkowski B, Makarewicz R. Pre-irradiation tumour volumes defined by MRI and dual time-point FET-PET for the prediction of glioblastoma multiforme recurrence: a prospective study. Radiother Oncol. 2016;120(2):241–7.
Moller S, Law I, Af Rosenschold PM, 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(1):132–7.
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.
Roelcke U, Wyss MT, Nowosielski M, Rudà 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 Oncol. 2016;18(5):744–51.
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.
Acknowledgment
Parts of this paper originate from the doctoral thesis of Isabel Winkelmann.
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Ethical approval of the retrospective study protocol was given by the institutional review board of the LMU (no. 606–16) in accordance with the ICH Guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki.
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All patients gave written informed consent prior to the PET examination.
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The original version of this article was revised: The name of M. Unterrainer was inadvertently presented as M. Unterrrainer in the original article.
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Unterrainer, M., Winkelmann, I., Suchorska, B. et al. Biological tumour volumes of gliomas in early and standard 20–40 min 18F-FET PET images differ according to IDH mutation status. Eur J Nucl Med Mol Imaging 45, 1242–1249 (2018). https://doi.org/10.1007/s00259-018-3969-4
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DOI: https://doi.org/10.1007/s00259-018-3969-4