Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[18F]fluoro-l-DOPA

Pretze, Marc; Franck, Dominic; Kunkel, F.; Foßhag, Erich; Wängler, Carmen; Wängler, Björn

doi:10.1016/j.nucmedbio.2016.10.007

Cited by 25 publications

(40 citation statements)

References 46 publications

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“…In addition, most cassette-based systems are not convenient platforms for synthesis development due to the need for cassette or software modifications and due to restricted access to the reaction mixture at intermediate steps. In contrast, the ELIXYS system has a unique design that provides a robust environment for carrying out reactions under more challenging conditions (20) and can perform synthesis protocols under conditions that lead to leaks or damage in other synthesis modules (21). Furthermore, it has features that facilitate synthesis development, including access to the reaction vessel contents for intermediate measurements and a drag-and-drop programming interface based on intuitive "unit operations" (22).…”

Section: Significancementioning

confidence: 99%

Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Collins

Waldmann

Drake

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.

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Section: Significancementioning

confidence: 99%

Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Collins

Waldmann

Drake

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…287,288 Pretze et al evaluated the [ 18 F]F-DOPA synthesis procedure, however was not able to synthesize [ 18 F]F-DOPA in the same radiochemical yield. 289 It was determined that this was caused by a combination of factors: (1) decomposition of the trimethyl ammonium triflate group of the precursor molecule into 274,[280][281][282][283][284][285][286][287][288] Scheme 91 C-C coupling and hydrolysis of a [ 18 F]fluorobenzyl halide with N-(diphenylmethylene)glycine tert-butyl ester and a phase transfer catalyst (PTC). 280,287,288 4-aminobenzaldehyde; (2) problematic automation due to formation of precipitates during the C-C coupling reaction.…”

Section: [ 18 F]fluorobenzaldehydesmentioning

confidence: 99%

“…With this method, [ 18 F]F-DOPA was synthesized in a radiochemical yield of 20 AE 1% (dc). 289 3.2.4.3 Application of [ 18 F]fluorobenzyl halides in alkylation of phospines and benzyl alcohols. Three new tracers have been synthesised using [ 18 F]fluorobenzyl halides since 2010 (Scheme 92).…”

Section: [ 18 F]fluorobenzaldehydesmentioning

confidence: 99%

Fluorine-18 labelled building blocks for PET tracer synthesis

et al. 2017

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Positron emission tomography (PET) is an important driver for present day healthcare. Fluorine-18 is the most widely used radioisotope for PET imaging and a thorough overview of the available radiochemistry methodology is a prerequisite for selection of a synthetic approach for new fluorine-18 labelled PET tracers. These PET tracers can be synthesised either by late-stage radiofluorination, introducing fluorine-18 in the last step of the synthesis, or by a building block approach (also called modular build-up approach), introducing fluorine-18 in a fast and efficient manner in a building block, which is reacted further in one or multiple reaction steps to form the PET tracer. This review presents a comprehensive overview of the synthesis and application of fluorine-18 labelled building blocks since 2010.

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“…On the other hand, this procedure is sensitive to the basic conditions of the 18 F-fluorination reaction, which can lead to an epimerization of the amino acid. In a recently published study on the nucleophilic synthesis of 6-[ 18 F]FDOPA both methods of carbonyl activated 18 F-exchange were compared, using the 3-and 5-step procedure [137]. It was convincingly shown that the three-step process was much easier and reliable to be automated, providing a RCY of 20 ± 1% within 114 min.…”

Section: Progress In Aromatic Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

“…In fact, there are rarely cases, where different methods were compared in one laboratory, like for [ 18 F]FLT [103,105] and 6-[ 18 F]FDOPA [137]. The latter is one of the few examples, where several labelling strategies were pursued with much effort and realised over the last three decades.…”

Section: Closing Remarksmentioning

confidence: 99%

18F-labelling innovations and their potential for clinical application

Coenen

Neumaier

2018

Clin Transl Imaging

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An impressive variety of new methodologies for the preparation of 18 F-labelled tracers and ligands has appeared over the last decade. Most strategies of the newly developed radiofluorination methods predominantly aim at products of high molar activity by 'late-stage' labelling of small (hetero)aromatic molecules and the use of transition metals. This is accompanied by the improvement of technical procedures, like preparation of reactive [ 18 F]fluoride and automated syntheses. The newly introduced procedures reflect a high innovative level and creativity in radio(pharmaceutical) chemistry at present, which are based on modern chemical methods and deep mechanistic insights. Taking also automation and quality control into consideration, major recently developed radiofluorination methods, most of those still under development, are compiled here in view of their potential for clinical PET imaging and thus the ability to advance molecular imaging.

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Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[18F]fluoro-l-DOPA

Cited by 25 publications

References 46 publications

Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Fluorine-18 labelled building blocks for PET tracer synthesis

18F-labelling innovations and their potential for clinical application

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Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[18F]fluoro-l-DOPA

Cited by 25 publications

References 46 publications

Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer

Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer

Fluorine-18 labelled building blocks for PET tracer synthesis

18F-labelling innovations and their potential for clinical application

Contact Info

Product

Resources

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Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer