New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma

The use of O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influ...

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Autores principales: Verhoeven, Jeroen, Hulpia, Fabian, Kersemans, Ken, Bolcaen, Julie, De Lombaerde, Stef, Goeman, Jan, Descamps, Benedicte, Hallaert, Giorgio, Van den Broecke, Caroline, Deblaere, Karel, Vanhove, Christian, Van der Eycken, Johan, Van Calenbergh, Serge, Goethals, Ingeborg, De Vos, Filip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393465/
https://www.ncbi.nlm.nih.gov/pubmed/30814660
http://dx.doi.org/10.1038/s41598-019-40013-x
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author Verhoeven, Jeroen
Hulpia, Fabian
Kersemans, Ken
Bolcaen, Julie
De Lombaerde, Stef
Goeman, Jan
Descamps, Benedicte
Hallaert, Giorgio
Van den Broecke, Caroline
Deblaere, Karel
Vanhove, Christian
Van der Eycken, Johan
Van Calenbergh, Serge
Goethals, Ingeborg
De Vos, Filip
author_facet Verhoeven, Jeroen
Hulpia, Fabian
Kersemans, Ken
Bolcaen, Julie
De Lombaerde, Stef
Goeman, Jan
Descamps, Benedicte
Hallaert, Giorgio
Van den Broecke, Caroline
Deblaere, Karel
Vanhove, Christian
Van der Eycken, Johan
Van Calenbergh, Serge
Goethals, Ingeborg
De Vos, Filip
author_sort Verhoeven, Jeroen
collection PubMed
description The use of O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro K(i) determination, the most promising compound, 2-[(18)F]-2-fluoroethyl-l-phenylalanine (2-[(18)F]FELP), was selected for further evaluation and in vitro comparison with [(18)F]FET. Subsequently, 2-[(18)F]FELP was assessed in vivo and compared with [(18)F]FET and [(18)F]FDG in a F98 glioblastoma rat model. 2-[(18)F]FELP showed improved in vitro characteristics over [(18)F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[(18)F]FELP is a promising new PET tracer for brain tumor imaging.
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spelling pubmed-63934652019-03-01 New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma Verhoeven, Jeroen Hulpia, Fabian Kersemans, Ken Bolcaen, Julie De Lombaerde, Stef Goeman, Jan Descamps, Benedicte Hallaert, Giorgio Van den Broecke, Caroline Deblaere, Karel Vanhove, Christian Van der Eycken, Johan Van Calenbergh, Serge Goethals, Ingeborg De Vos, Filip Sci Rep Article The use of O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro K(i) determination, the most promising compound, 2-[(18)F]-2-fluoroethyl-l-phenylalanine (2-[(18)F]FELP), was selected for further evaluation and in vitro comparison with [(18)F]FET. Subsequently, 2-[(18)F]FELP was assessed in vivo and compared with [(18)F]FET and [(18)F]FDG in a F98 glioblastoma rat model. 2-[(18)F]FELP showed improved in vitro characteristics over [(18)F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[(18)F]FELP is a promising new PET tracer for brain tumor imaging. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393465/ /pubmed/30814660 http://dx.doi.org/10.1038/s41598-019-40013-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Verhoeven, Jeroen
Hulpia, Fabian
Kersemans, Ken
Bolcaen, Julie
De Lombaerde, Stef
Goeman, Jan
Descamps, Benedicte
Hallaert, Giorgio
Van den Broecke, Caroline
Deblaere, Karel
Vanhove, Christian
Van der Eycken, Johan
Van Calenbergh, Serge
Goethals, Ingeborg
De Vos, Filip
New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title_full New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title_fullStr New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title_full_unstemmed New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title_short New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma
title_sort new fluoroethyl phenylalanine analogues as potential lat1-targeting pet tracers for glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393465/
https://www.ncbi.nlm.nih.gov/pubmed/30814660
http://dx.doi.org/10.1038/s41598-019-40013-x
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