Dataset Information

Automated radiosynthesis of two ¹⁸F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [¹⁸F]FMISO and [¹⁸F]PM-PBB3, via [¹⁸F]epifluorohydrin.

ABSTRACT:

Background

[¹⁸F]Fluoromisonidazole ([¹⁸F]FMISO) and 1-[¹⁸F]fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸F]PM-PBB3 or [¹⁸F]APN-1607) are clinically used radiotracers for imaging hypoxia and tau pathology, respectively. Both radiotracers were produced by direct ¹⁸F-fluorination using the corresponding tosylate precursors 1 or 2 and [¹⁸F]F^-, followed by the removal of protecting groups. In this study, we synthesized [¹⁸F]FMISO and [¹⁸F]PM-PBB3 by ¹⁸F-fluoroalkylation using [¹⁸F]epifluorohydrin ([¹⁸F]5) for clinical applications.

Results

First, [¹⁸F]5 was synthesized by the reaction of 1,2-epoxypropyl tosylate (8) with [¹⁸F]F^- and was purified by distillation. Subsequently, [¹⁸F]5 was reacted with 2-nitroimidazole (6) or PBB3 (7) as a precursor for ¹⁸F-labeling, and each reaction mixture was purified by preparative high-performance liquid chromatography and formulated to obtain the [¹⁸F]FMISO or [¹⁸F]PM-PBB3 injection. All synthetic sequences were performed using an automated ¹⁸F-labeling synthesizer. The obtained [¹⁸F]FMISO showed sufficient radioactivity (0.83 ± 0.20 GBq at the end of synthesis (EOS); n = 8) with appropriate radiochemical yield based on [¹⁸F]F^- (26 ± 7.5 % at EOS, decay-corrected; n = 8). The obtained [¹⁸F]PM-PBB3 also showed sufficient radioactivity (0.79 ± 0.10 GBq at EOS; n = 11) with appropriate radiochemical yield based on [¹⁸F]F^- (16 ± 3.2 % at EOS, decay-corrected; n = 11).

Conclusions

Both [¹⁸F]FMISO and [¹⁸F]PM-PBB3 injections were successfully synthesized with sufficient radioactivity by ¹⁸F-fluoroalkylation using [¹⁸F]5.

SUBMITTER: Ohkubo T

PROVIDER: S-EPMC8272768 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionGlucose 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 [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine.Materials and methodsBoth tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [3H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model.ResultsThe radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18% (n = 10) ([18F]fluorophenylglutamine) and 8.05 ± 3.25% (n = 5) ([18F]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 [18F]FBPG in the mice PC-3 xenograft and a moderate uptake of [18F]FPG in the PC-3 tumors.ConclusionWe investigated the imaging potential of two novel PET radiotracers [18F]FPG and [18F]FBPG. [18F]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 [18F]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. (2S,4R)4-[18F]fluoroglutamine). [18F]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.

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Dataset Information

Automated radiosynthesis of two ¹⁸F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [¹⁸F]FMISO and [¹⁸F]PM-PBB3, via [¹⁸F]epifluorohydrin.

Background

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin.

Background

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Automated radiosynthesis of two ¹⁸F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [¹⁸F]FMISO and [¹⁸F]PM-PBB3, via [¹⁸F]epifluorohydrin.