Automation for Optimised Production of Fluorine-18-Labelled Radiopharmaceuticals

Sachinidis, John; Poniger, Stan; Tochon-Danguy, Henri

doi:10.2174/1874471011003030248

Cited by 14 publications

(7 citation statements)

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“…2-[ 18 F]fluoro-2-deoxy- d -glucose ([ 18 F]FDG) is the most commonly utilized PET tracer due to its relative ease of production, manageable half-life, and ubiquitous application [2,3]. The increased demand for [ 18 F]FDG has led to the development of many automated radiosynthesizers to lower its cost, enable its production at many different sites, and reduce the radiation exposure to the radiochemist [4,5]. …”

Section: Introductionmentioning

confidence: 99%

ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers

et al. 2013

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BackgroundAutomated radiosynthesizers are vital for routine production of positron-emission tomography tracers to minimize radiation exposure to operators and to ensure reproducible synthesis yields. The recent trend in the synthesizer industry towards the use of disposable kits aims to simplify setup and operation for the user, but often introduces several limitations related to temperature and chemical compatibility, thus requiring reoptimization of protocols developed on non-cassette-based systems. Radiochemists would benefit from a single hybrid system that provides tremendous flexibility for development and optimization of reaction conditions while also providing a pathway to simple, cassette-based production of diverse tracers.MethodsWe have designed, built, and tested an automated three-reactor radiosynthesizer (ELIXYS) to provide a flexible radiosynthesis platform suitable for both tracer development and routine production. The synthesizer is capable of performing high-pressure and high-temperature reactions by eliminating permanent tubing and valve connections to the reaction vessel. Each of the three movable reactors can seal against different locations on disposable cassettes to carry out different functions such as sealed reactions, evaporations, and reagent addition. A reagent and gas handling robot moves sealed reagent vials from storage locations in the cassette to addition positions and also dynamically provides vacuum and inert gas to ports on the cassette. The software integrates these automated features into chemistry unit operations (e.g., React, Evaporate, Add) to intuitively create synthesis protocols. 2-Deoxy-2-[18F]fluoro-5-methyl-β-l-arabinofuranosyluracil (l-[18F]FMAU) and 2-deoxy-2-[18F]fluoro-β-d-arabinofuranosylcytosine (d-[18F]FAC) were synthesized to validate the system.Resultsl-[18F]FMAU and d-[18F]FAC were successfully synthesized in 165 and 170 min, respectively, with decay-corrected radiochemical yields of 46% ± 1% (n = 6) and 31% ± 5% (n = 6), respectively. The yield, repeatability, and synthesis time are comparable to, or better than, other reports. d-[18F]FAC produced by ELIXYS and another manually operated apparatus exhibited similar biodistribution in wild-type mice.ConclusionThe ELIXYS automated radiosynthesizer is capable of performing radiosyntheses requiring demanding conditions: up to three reaction vessels, high temperatures, high pressures, and sensitive reagents. Such flexibility facilitates tracer development and the ability to synthesize multiple tracers on the same system without customization or replumbing. The disposable cassette approach simplifies the transition from development to production.

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Section: Introductionmentioning

confidence: 99%

ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers

et al. 2013

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“…A special type of synthesis device is the hardware kit system, also called "cassette system" [201]. All reagents, which are needed thereby for radiofluorination, are prefabricated and enclosed in disposable cassettes, which are easily switched on the synthesis device.…”

Section: Automation Of Nucleophilic 18 F-fluorinationmentioning

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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“…The preparation of positron emission tomography (PET) tracers has evolved over the years to include increasing automation (Alexoff, 2003;Keng et al, 2012;Krasikova, 2007). For automation to be successful, however, thorough characterization of the reagent delivery, reaction, solution transfer, and other mechanisms of the radiosynthesizer needs to be performed and understood (Sachinidis et al, 2010). Only then is one able to specify appropriate parameters for the automated radiosynthesis protocol such that the system consistently and efficiently produces the desired product from a given input of reagents.…”

Section: Introductionmentioning

confidence: 99%

Understanding temperatures and pressures during short radiochemical reactions

Lazari¹,

Irribarren²,

Zhang³

et al. 2016

Applied Radiation and Isotopes

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Automated radiosynthesizers are critical for the reliable, routine production of PET tracers. To perform reactions in these systems, the temperature of the reactor heater is controlled, and the liquid temperature within the reaction vessel is presumed to closely follow. In reality, the liquid temperature can lag by several minutes and generally does not reach the heater temperature. Furthermore, because different synthesizers have different heating mechanisms and geometries, discrepancies are certain to exist between the actual temperatures experienced by the reaction mixture on different synthesizers. For dissimilar reactors, this can necessitate re-optimization of conditions when adapting a synthesis from one system to another, especially for the short-duration reactions common in radiochemistry. Herein, we study the relationship between the temperatures of the reactor heater and reaction liquid for various solvents using the ELIXYS radiosynthesizer as a representative example of a vial-based system. Our aims are to quantitatively illustrate this discrepancy to the community and provide data necessary to enable efficient translation of protocols between other radiosynthesizers and the ELIXYS.

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Automation for Optimised Production of Fluorine-18-Labelled Radiopharmaceuticals

Cited by 14 publications

References 0 publications

ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers

ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers

18F-labelling innovations and their potential for clinical application

Understanding temperatures and pressures during short radiochemical reactions

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