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 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.