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• W3005981972 abstract "Abstract Introduction Glucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors. We elaborated on the glutamine-derived PET tracers by developing two novel probes, namely [ 18 F]fluorophenylglutamine and [ 18 F]fluorobiphenylglutamine Materials and methods Both tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [ 3 H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [ 18 F]fluorophenylglutamine and [ 18 F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model. Results The radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18 % (n=10) ([ 18 F]fluorophenylglutamine) and 8.05 ± 3.25 % (n=5) ([ 18 F]fluorobiphenylglutamine). In vitro inhibition experiments showed a moderate and low affinity of fluorophenylglutamine and fluorobiphenylglutamine, respectively, towards the human ASCT-2 transporter. Both compounds had a low affinity towards the rat ASCT-2 transporter. These results were endorsed by the in vivo experiments with low uptake of both tracers in the F98 rat xenograft, low uptake of [ 18 F]FBPG in the mice PC-3 xenograft and a moderate uptake of [ 18 F]FPG in the PC-3 tumors. Conclusion We investigated the imaging potential of two novel PET radiotracers [ 18 F]FPG and [ 18 F]FBPG. [ 18 F]FPG is the first example of a glutamine radiotracer derivatized with a phenyl group which enables the exploration of further derivatization of the phenyl group to increase the affinity and imaging qualities. We hypothesize that increasing the affinity of [ 18 F]FPG by optimizing the substituents of the arene ring can result in a high-quality glutamine-based PET radiotracer. Advances in Knowledge and Implications for patient care We hereby report novel glutamine-based PET-tracers. These tracers are tagged on the arene group with fluorine-18, hereby preventing in vivo defluorination, which can occur with alkyl labelled tracers (e.g. (2 S ,4 R )4-[ 18 F]fluoroglutamine). [ 18 F]FPG shows clear tumor uptake in vivo , has no in vivo defluorination and has a straightforward production. We believe this tracer is a good starting point for the development of a high-quality tracer which is useful for the clinical visualization of the glutamine transport." @default.
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• W3005981972 date "2020-02-15" @default.
• W3005981972 modified "2023-10-05" @default.
• W3005981972 title "Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine" @default.
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• W3005981972 doi "https://doi.org/10.1101/2020.02.14.948372" @default.
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