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.