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Published in: EJNMMI Research 1/2018

Open Access 01-12-2018 | Original research

Quantification of O-(2-[18F]fluoroethyl)-L-tyrosine kinetics in glioma

Authors: Thomas Koopman, Niels Verburg, Robert C. Schuit, Petra J. W. Pouwels, Pieter Wesseling, Albert D. Windhorst, Otto S. Hoekstra, Philip C. de Witt Hamer, Adriaan A. Lammertsma, Ronald Boellaard, Maqsood Yaqub

Published in: EJNMMI Research | Issue 1/2018

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Abstract

Background

This study identified the optimal tracer kinetic model for quantification of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET) studies in seven patients with diffuse glioma (four glioblastoma, three lower grade glioma). The performance of more simplified approaches was evaluated by comparison with the optimal compartment model. Additionally, the relationship with cerebral blood flow—determined by [15O]H2O PET—was investigated.

Results

The optimal tracer kinetic model was the reversible two-tissue compartment model. Agreement analysis of binding potential estimates derived from reference tissue input models with the distribution volume ratio (DVR)-1 derived from the plasma input model showed no significant average difference and limits of agreement of − 0.39 and 0.37. Given the range of DVR-1 (− 0.25 to 1.5), these limits are wide. For the simplified methods, the 60–90 min tumour-to-blood ratio to parent plasma concentration yielded the highest correlation with volume of distribution VT as calculated by the plasma input model (r = 0.97). The 60–90 min standardized uptake value (SUV) showed better correlation with VT (r = 0.77) than SUV based on earlier intervals. The 60–90 min SUV ratio to contralateral healthy brain tissue showed moderate agreement with DVR with no significant average difference and limits of agreement of − 0.24 and 0.30. A significant but low correlation was found between VT and CBF in the tumour regions (r = 0.61, p = 0.007).

Conclusion

Uptake of [18F]FET was best modelled by a reversible two-tissue compartment model. Reference tissue input models yielded estimates of binding potential which did not correspond well with plasma input-derived DVR-1. In comparison, SUV ratio to contralateral healthy brain tissue showed slightly better performance, if measured at the 60–90 min interval. SUV showed only moderate correlation with VT. VT shows correlation with CBF in tumour.
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Literature
1.
go back to reference Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl med off Publ Soc Nucl Med. 1999;40(1):205–12. Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl med off Publ Soc Nucl Med. 1999;40(1):205–12.
2.
go back to reference Langen K-J, Stoffels G, Filss C, Heinzel A, Stegmayr C, Lohmann P, et al. Imaging of amino acid transport in brain tumours: positron emission tomography with O-(2-[ 18 F]fluoroethyl)- L -tyrosine (FET). Methods. 2017;130:124–34 Langen K-J, Stoffels G, Filss C, Heinzel A, Stegmayr C, Lohmann P, et al. Imaging of amino acid transport in brain tumours: positron emission tomography with O-(2-[ 18 F]fluoroethyl)- L -tyrosine (FET). Methods. 2017;130:124–34
3.
go back to reference Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R. Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. J Nucl med off Publ Soc Nucl Med 1999;40(8):1367–1373. Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R. Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. J Nucl med off Publ Soc Nucl Med 1999;40(8):1367–1373.
4.
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-Oncologia. 2016;18(9):1199–208.CrossRef 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-Oncologia. 2016;18(9):1199–208.CrossRef
6.
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
7.
go back to reference Langen K-J, 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(4):167–73.CrossRefPubMed Langen K-J, 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(4):167–73.CrossRefPubMed
8.
go back to reference Bolcaen J, Lybaert K, Moerman L, Descamps B, Deblaere K, Boterberg T, et al. Kinetic modeling and graphical analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between high-grade glioma and radiation necrosis in rats. Gelovani JG, editor. PLoS ONE 2016;11(8):e0161845. Bolcaen J, Lybaert K, Moerman L, Descamps B, Deblaere K, Boterberg T, et al. Kinetic modeling and graphical analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between high-grade glioma and radiation necrosis in rats. Gelovani JG, editor. PLoS ONE 2016;11(8):e0161845.
9.
go back to reference Richard MA, Fouquet JP, Lebel R, Lepage M. Determination of an optimal pharmacokinetic model of 18 F-FET for quantitative applications in rat brain tumors. J Nucl Med. 2017;58(8):1278–84.CrossRefPubMed Richard MA, Fouquet JP, Lebel R, Lepage M. Determination of an optimal pharmacokinetic model of 18 F-FET for quantitative applications in rat brain tumors. J Nucl Med. 2017;58(8):1278–84.CrossRefPubMed
10.
go back to reference Kratochwil C, Combs SE, Leotta K, Afshar-Oromieh A, Rieken S, Debus J, et al. Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent brain tumors. Neuro-Oncologia. 2014;16(3):434–40.CrossRef Kratochwil C, Combs SE, Leotta K, Afshar-Oromieh A, Rieken S, Debus J, et al. Intra-individual comparison of 18F-FET and 18F-DOPA in PET imaging of recurrent brain tumors. Neuro-Oncologia. 2014;16(3):434–40.CrossRef
11.
go back to reference Thiele F, Ehmer J, Piroth MD, Eble MJ, Coenen HH, Kaiser H-J, et al. The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma. Phys Med Biol. 2009;54(18):5525–39.CrossRefPubMed Thiele F, Ehmer J, Piroth MD, Eble MJ, Coenen HH, Kaiser H-J, et al. The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma. Phys Med Biol. 2009;54(18):5525–39.CrossRefPubMed
12.
go back to reference Loeb R, Navab N, Ziegler SI. Direct parametric reconstruction using anatomical regularization for simultaneous PET/MRI data. IEEE Trans Med Imaging. 2015;34(11):2233–47.CrossRefPubMed Loeb R, Navab N, Ziegler SI. Direct parametric reconstruction using anatomical regularization for simultaneous PET/MRI data. IEEE Trans Med Imaging. 2015;34(11):2233–47.CrossRefPubMed
13.
go back to reference Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Müller H-W, et al. Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-l-tyrosine. Eur J Nucl Med Mol Imaging. 2003;30(4):519–24.CrossRefPubMed Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Müller H-W, et al. Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-l-tyrosine. Eur J Nucl Med Mol Imaging. 2003;30(4):519–24.CrossRefPubMed
14.
go back to reference Verburg N, Pouwels PJW, Boellaard R, Barkhof F, Hoekstra OS, Reijneveld JC, et al. Accurate delineation of glioma infiltration by advanced PET/MR neuro-imaging (FRONTIER study): a diagnostic study protocol. Neurosurgery. 2016;79(4):535–40.CrossRefPubMed Verburg N, Pouwels PJW, Boellaard R, Barkhof F, Hoekstra OS, Reijneveld JC, et al. Accurate delineation of glioma infiltration by advanced PET/MR neuro-imaging (FRONTIER study): a diagnostic study protocol. Neurosurgery. 2016;79(4):535–40.CrossRefPubMed
15.
go back to reference Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. Revised 4th edition. Lyon: International Agency for Research on Cancer; 2016. 408 p. (World Health Organization classification of tumours). Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. Revised 4th edition. Lyon: International Agency for Research on Cancer; 2016. 408 p. (World Health Organization classification of tumours).
16.
go back to reference Zuhayra M, Alfteimi A, Forstner CV, Lützen U, Meller B, Henze E. New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: simple, fast, and high yielding automated synthesis. Bioorg Med Chem. 2009;17(21):7441–8.CrossRefPubMed Zuhayra M, Alfteimi A, Forstner CV, Lützen U, Meller B, Henze E. New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: simple, fast, and high yielding automated synthesis. Bioorg Med Chem. 2009;17(21):7441–8.CrossRefPubMed
17.
go back to reference Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, et al. Tracer kinetic modeling of the 5-HT1AReceptor ligand [carbonyl-11C]WAY-100635 for PET. NeuroImage. 1998;8(4):426–40.CrossRefPubMed Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, et al. Tracer kinetic modeling of the 5-HT1AReceptor ligand [carbonyl-11C]WAY-100635 for PET. NeuroImage. 1998;8(4):426–40.CrossRefPubMed
18.
go back to reference Boellaard R, Knaapen P, Rijbroek A, Luurtsema GJJ, Lammertsma AA. Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and positron emission tomography. Mol Imaging Biol. 2005;7(4):273–85.CrossRefPubMed Boellaard R, Knaapen P, Rijbroek A, Luurtsema GJJ, Lammertsma AA. Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and positron emission tomography. Mol Imaging Biol. 2005;7(4):273–85.CrossRefPubMed
19.
go back to reference Gunn RN, Gunn SR, Cunningham VJ. Positron emission tomography compartmental models. J Cereb Blood Flow Metab. 2001;21(6):635–52.CrossRefPubMed Gunn RN, Gunn SR, Cunningham VJ. Positron emission tomography compartmental models. J Cereb Blood Flow Metab. 2001;21(6):635–52.CrossRefPubMed
20.
go back to reference Yaqub M, Boellaard R, Kropholler MA, Lammertsma AA. Optimization algorithms and weighting factors for analysis of dynamic PET studies. Phys Med Biol. 2006;51(17):4217.CrossRefPubMed Yaqub M, Boellaard R, Kropholler MA, Lammertsma AA. Optimization algorithms and weighting factors for analysis of dynamic PET studies. Phys Med Biol. 2006;51(17):4217.CrossRefPubMed
21.
go back to reference Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19(6):716–23.CrossRef Akaike H. A new look at the statistical model identification. IEEE Trans Autom Control. 1974;19(6):716–23.CrossRef
22.
go back to reference Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27(9):1533–9.CrossRefPubMed Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27(9):1533–9.CrossRefPubMed
23.
go back to reference Blomqvist G, Pauli S, Farde L, Eriksson L, Persson A, Halldin C. Maps of receptor binding parameters in the human brain? A kinetic analysis of PET measurements. Eur J Nucl Med. 1990;16(4–6):257–65.CrossRefPubMed Blomqvist G, Pauli S, Farde L, Eriksson L, Persson A, Halldin C. Maps of receptor binding parameters in the human brain? A kinetic analysis of PET measurements. Eur J Nucl Med. 1990;16(4–6):257–65.CrossRefPubMed
24.
go back to reference Cunningham VJ, Hume SP, Price GR, Ahier RG, Cremer JE, Jones AK. Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro. J Cereb Blood Flow Metab. 1991;11(1):1–9.CrossRefPubMed Cunningham VJ, Hume SP, Price GR, Ahier RG, Cremer JE, Jones AK. Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro. J Cereb Blood Flow Metab. 1991;11(1):1–9.CrossRefPubMed
25.
go back to reference Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. NeuroImage. 1996;4(3 Pt 1):153–8.CrossRefPubMed Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. NeuroImage. 1996;4(3 Pt 1):153–8.CrossRefPubMed
26.
go back to reference Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999;8(2):135–60.CrossRefPubMed Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999;8(2):135–60.CrossRefPubMed
27.
go back to reference Salinas CA, Searle GE, Gunn RN. The simplified reference tissue model: model assumption violations and their impact on binding potential. J Cereb Blood Flow Metab. 2015;35(2):304–11.CrossRefPubMed Salinas CA, Searle GE, Gunn RN. The simplified reference tissue model: model assumption violations and their impact on binding potential. J Cereb Blood Flow Metab. 2015;35(2):304–11.CrossRefPubMed
Metadata
Title
Quantification of O-(2-[18F]fluoroethyl)-L-tyrosine kinetics in glioma
Authors
Thomas Koopman
Niels Verburg
Robert C. Schuit
Petra J. W. Pouwels
Pieter Wesseling
Albert D. Windhorst
Otto S. Hoekstra
Philip C. de Witt Hamer
Adriaan A. Lammertsma
Ronald Boellaard
Maqsood Yaqub
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-018-0418-0

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