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 in...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-02, Vol.9 (1), p.2878-2878, Article 2878
Main Authors: 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
Format: Article
Language:English
Subjects:
140/131
59/57
59/78
631/67/2321
639/638/309/2420
639/638/903
692/4028/67/2321
Affinity
Amino acids
Brain cancer
Brain tumors
Glioblastoma
Humanities and Social Sciences
Medical imaging
multidisciplinary
Neuroimaging
Phenylalanine
Positron emission tomography
Science
Science (multidisciplinary)
Stereospecificity
Tracers
Tyrosine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-40013-x