Skip to main content
Top
Published in: EJNMMI Research 1/2017

Open Access 01-12-2017 | Original research

Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

Authors: Marcus Unterrainer, Franziska Vettermann, Matthias Brendel, Adrien Holzgreve, Michael Lifschitz, Matthias Zähringer, Bogdana Suchorska, Vera Wenter, Ben M. Illigens, Peter Bartenstein, Nathalie L. Albert

Published in: EJNMMI Research | Issue 1/2017

Login to get access

Abstract

Background

PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading.
The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.

Results

Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.

Conclusions

The commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.
Literature
1.
go back to reference 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. now058.CrossRefPubMed 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. now058.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
3.
go back to reference 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. 2016:10.2967/jnumed.115.171033. 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. 2016:10.​2967/​jnumed.​115.​171033.
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F] fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42(5):685–95.CrossRefPubMed Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F] fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42(5):685–95.CrossRefPubMed
7.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference Unterrainer M, Suchorska B, Biczok A, Bartenstein P, Kreth F-W, Albert N. Value of 18F-FET PET for chemotherapy monitoring in non-contrast enhancing gliomas. J Nucl Med. 2016;57(supplement 2):14. Unterrainer M, Suchorska B, Biczok A, Bartenstein P, Kreth F-W, Albert N. Value of 18F-FET PET for chemotherapy monitoring in non-contrast enhancing gliomas. J Nucl Med. 2016;57(supplement 2):14.
10.
go back to reference 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 Oncol. 2015;17(9):1293–300. nov088.PubMedPubMedCentral 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 Oncol. 2015;17(9):1293–300. nov088.PubMedPubMedCentral
11.
go back to reference Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, et al. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017;19(2):281–8. Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, et al. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017;19(2):281–8.
12.
go back to reference Galldiks N, Stoffels G, Filss CP, Piroth MD, Sabel M, Ruge MI, et al. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. J Nucl Med. 2012;53(9):1367–74.CrossRefPubMed Galldiks N, Stoffels G, Filss CP, Piroth MD, Sabel M, Ruge MI, et al. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. J Nucl Med. 2012;53(9):1367–74.CrossRefPubMed
13.
go back to reference Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn J-C, Nachbichler SB, et al. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18 F] FET-PET overcome diagnostic uncertainties? Radiat Oncol. 2016;11(1):139.CrossRefPubMedPubMedCentral Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn J-C, Nachbichler SB, et al. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18 F] FET-PET overcome diagnostic uncertainties? Radiat Oncol. 2016;11(1):139.CrossRefPubMedPubMedCentral
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.PubMed 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.PubMed
16.
go back to reference 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 Oncol. 2013;15(3):341–51.CrossRefPubMedPubMedCentral 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 Oncol. 2013;15(3):341–51.CrossRefPubMedPubMedCentral
17.
go back to reference Langen KJ, Bartenstein P, Boecker H, Brust P, Coenen HH, Drzezga A, et al. PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren. Nuklearmedizin. 2011;50(4):167–73.CrossRefPubMed Langen KJ, Bartenstein P, Boecker H, Brust P, Coenen HH, Drzezga A, et al. PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren. Nuklearmedizin. 2011;50(4):167–73.CrossRefPubMed
18.
go back to reference Lohmann P, Stoffels G, Ceccon G, Rapp M, Sabel M, Filss CP, et al. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans. Eur Radiol. 2016. [Epub ahead of print]. Lohmann P, Stoffels G, Ceccon G, Rapp M, Sabel M, Filss CP, et al. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans. Eur Radiol. 2016. [Epub ahead of print].
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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 Oncol. 2015;17(5):757–63.CrossRefPubMed 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 Oncol. 2015;17(5):757–63.CrossRefPubMed
21.
go back to reference Coope DJ, Čížek J, Eggers C, Vollmar S, Heiss W-D, Herholz K. Evaluation of primary brain tumors using 11C-methionine PET with reference to a normal methionine uptake map. J Nucl Med. 2007;48(12):1971–80.CrossRefPubMed Coope DJ, Čížek J, Eggers C, Vollmar S, Heiss W-D, Herholz K. Evaluation of primary brain tumors using 11C-methionine PET with reference to a normal methionine uptake map. J Nucl Med. 2007;48(12):1971–80.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller H-W, et al. O-(2-[18F] fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128(3):678–87.CrossRefPubMed Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller H-W, et al. O-(2-[18F] fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128(3):678–87.CrossRefPubMed
24.
go back to reference Piroth MD, Galldiks N, Pinkawa M, Holy R, Stoffels G, Ermert J, et al. Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume. Radiat Oncol. 2016;11(1):87.CrossRefPubMedPubMedCentral Piroth MD, Galldiks N, Pinkawa M, Holy R, Stoffels G, Ermert J, et al. Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume. Radiat Oncol. 2016;11(1):87.CrossRefPubMedPubMedCentral
25.
go back to reference Langen K-J, Watts C. Neuro-oncology: amino acid PET for brain tumours [mdash] ready for the clinic? Nat Rev Neurol. 2016;12(7):375–6.CrossRefPubMed Langen K-J, Watts C. Neuro-oncology: amino acid PET for brain tumours [mdash] ready for the clinic? Nat Rev Neurol. 2016;12(7):375–6.CrossRefPubMed
26.
go back to reference Watts C, Langen K-J. PET imaging in glioma: is it time for mainstream practice? Neuro Oncol. 2016;18(9):1193–4.CrossRefPubMed Watts C, Langen K-J. PET imaging in glioma: is it time for mainstream practice? Neuro Oncol. 2016;18(9):1193–4.CrossRefPubMed
Metadata
Title
Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?
Authors
Marcus Unterrainer
Franziska Vettermann
Matthias Brendel
Adrien Holzgreve
Michael Lifschitz
Matthias Zähringer
Bogdana Suchorska
Vera Wenter
Ben M. Illigens
Peter Bartenstein
Nathalie L. Albert
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2017
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-017-0295-y

Other articles of this Issue 1/2017

EJNMMI Research 1/2017 Go to the issue