High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress

Wang, J.; Dam, R. Michael van

doi:10.1177/1536012120973099

Cited by 18 publications

(24 citation statements)

References 80 publications

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“…The current trend in technology aiming to achieve even more compact systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production, in order to improve performance and minimize chemical and radiological risks [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. In this view, a latest generation device, the membrane-based Liquid–Liquid separator, 10 September ( Figure 1 ), patented and produced by ZAIPUT Flow Technologies company (Cambridge, MA, USA), has been recently used for the radiochemical separation of radioisotopes of nuclear medical interest [ 23 , 29 , 30 , 32 ], for the miniaturization of liquid–liquid extraction processes in an in-flow chemistry regime.…”

Section: Introductionmentioning

confidence: 99%

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum

et al. 2021

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The trend to achieve even more compact-sized systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production. Technetium-99m extraction from both high and low specific activity molybdenum could be simply performed by MEK-driven solvent extraction if it were not for unpractical automation. The aim of this work is to develop a solvent extraction and separation process of technetium from molybdenum in a micro-scale in-flow chemistry regime with the aid of a capillary loop and a membrane-based separator, respectively. The developed system is able to extract and separate quantitatively and selectively (91.0 ± 1.8% decay corrected) the [99mTc]TcO4Na in about 20 min, by using a ZAIPUT separator device. In conclusion, we demonstrated for the first time in our knowledge the high efficiency of a MEK-based solvent extraction process of 99mTc from a molybdenum-based liquid phased in an in-flow micro-scale regime.

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Section: Introductionmentioning

confidence: 99%

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum

et al. 2021

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“…New technologies like microfluidic “lab-on-a-chip” devices which have been exemplified for metal-based radiochemistry may provide automated radiochemistry and quality control on a single, inexpensive device for clinical use (He et al 2017 , 2016 ; Zhang et al 2020 ). These devices may also serve to improve the issues of fluoride concentration and efficiency of [ 18 F]AlF labelling (He et al 2014 ; Wang and Dam 2020 ). While these are not fully established and are not yet commercially available, they may serve to bring safe, standardised and automated GMP production to facilities with less extensive infrastructure, staffed by nuclear medicine technologists.…”

Section: Current and Future Perspectives On The [ 18 F]alf Methodsmentioning

confidence: 99%

The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules

Archibald

Allott

2021

EJNMMI radiopharm. chem.

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The aluminium-[18F]fluoride ([18F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [18F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [18F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method.

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“…Recent advancements in PET radiochemistry directed at development of batch-on-demand systems are creating new possibilities to expand availability of diverse diagnostic radiopharmaceuticals at low cost. Microfluidics offers a promising approach to enable economic production of one to a few patient doses due to advantages such as reduced (10–100×) reagent consumption, faster reaction kinetics, improved product yields, and reduced equipment footprint and shielding size 19 – 24 . Numerous reports have established the feasibility of synthesizing various radiopharmaceuticals using microfluidic synthesizers.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous reports have established the feasibility of synthesizing various radiopharmaceuticals using microfluidic synthesizers. However, due to the disparity between the volume of radioisotope solutions (~ 1 mL) and reaction volumes of microscale systems (as low as 1–10 s of µL), relatively small amounts of product activity have been acquired, suitable only for preclinical imaging 19 , 24 , 25 . Nevertheless, clinically-relevant quantities of various diagnostic radiopharmaceuticals has been produced with such microscale systems: [ 13 N]NH 3 26 , [ 68 Ga]Ga-PSMA-11 27 , [ 89 Zr]Zr-DFO-Trastuzamab 28 , [ 18 F]FDG 29 , 30 , [ 18 F]FET 31 , [ 18 F]fallypride 32 , 33 , [ 18 F]FT807 34 , [ 18 F]FPEB 35 , [ 18 F]FLT 36 and [ 18 F]FMISO 36 , 37 .…”

Section: Introductionmentioning

confidence: 99%

“…Microfluidic reactors can be classified in two categories: continuous-flow synthesizers, where the reaction volume is flowed through a microchannel or capillary, and batch-mode synthesizers, that contain a fixed reaction volume confined within a miniature reaction chamber 38 or within an isolated droplet 19 , 21 . In the continuous-flow systems, radioisotope and precursor solution streams are mixed prior to entering the heated reaction zone.…”

Section: Introductionmentioning

confidence: 99%

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Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use

Lisova

Wang

Hajagos

et al. 2021

Sci Rep

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Current equipment and methods for preparation of radiopharmaceuticals for positron emission tomography (PET) are expensive and best suited for large-scale multi-doses batches. Microfluidic radiosynthesizers have been shown to provide an economic approach to synthesize these compounds in smaller quantities, but can also be scaled to clinically-relevant levels. Batch microfluidic approaches, in particular, offer significant reduction in system size and reagent consumption. Here we show a simple and rapid technique to concentrate the radioisotope, prior to synthesis in a droplet-based radiosynthesizer, enabling production of clinically-relevant batches of [18F]FET and [18F]FBB. The synthesis was carried out with an automated synthesizer platform based on a disposable Teflon-silicon surface-tension trap chip. Up to 0.1 mL (4 GBq) of radioactivity was used per synthesis by drying cyclotron-produced aqueous [18F]fluoride in small increments directly inside the reaction site. Precursor solution (10 µL) was added to the dried [18F]fluoride, the reaction chip was heated for 5 min to perform radiofluorination, and then a deprotection step was performed with addition of acid solution and heating. The product was recovered in 80 µL volume and transferred to analytical HPLC for purification. Purified product was formulated via evaporation and resuspension or a micro-SPE formulation system. Quality control testing was performed on 3 sequential batches of each tracer. The method afforded production of up to 0.8 GBq of [18F]FET and [18F]FBB. Each production was completed within an hour. All batches passed quality control testing, confirming suitability for human use. In summary, we present a simple and efficient synthesis of clinically-relevant batches of [18F]FET and [18F]FBB using a microfluidic radiosynthesizer. This work demonstrates that the droplet-based micro-radiosynthesizer has a potential for batch-on-demand synthesis of 18F-labeled radiopharmaceuticals for human use.

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High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress

Cited by 18 publications

References 80 publications

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of 99mTc from Molybdenum

The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules

Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use

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