Microfluidic synthesis of radiotracers: recent developments and commercialization prospects

Mc Veigh, Mark; Bellan, Leon M.

doi:10.1039/d3lc00779k

Cited by 4 publications

(1 citation statement)

References 146 publications

(280 reference statements)

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“…However, many clinics have limited access to radiotracers to meet the immediate needs of their patients, and some specialized tracers may not be accessible due to the short half-life of radionuclides (Carbon-11; 20.34 min) [ 6 , 7 ]. The need for advanced, automated, and efficient radiotracer production has driven the development of innovative microfluidic techniques, offering promising solutions to overcome the existing challenges and fill the gap [ 8 ]. Microfluidic techniques offer significant advantages by enabling real-time and patient-specific radiotracer production such as the dose-on-demand approach [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline

Mallapura,

Tanguy,

Mahfuz

et al. 2024

Pharmaceuticals

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Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[11C]methionine and [11C]choline, was performed, using a microfluidic cassette and an iMiDEVTM module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[11C]methionine and [11C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [11C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[11C]methionine and >60% for [11C]choline (n = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[11C]methionine and [11C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields.

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Section: Introductionmentioning

confidence: 99%

Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline

Mallapura,

Tanguy,

Mahfuz

et al. 2024

Pharmaceuticals

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Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Scott,

Penuelas,

Rey

et al. 2024

EJNMMI radiopharm. chem.

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Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body This selection of highlights provides commentary on 19 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

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Production of [18F]DPA-714, [18F]fallypride and [18F]LBT-999 using iMiDEV, a fully automated microfluidic platform: towards clinical radiopharmaceutical production

Lahdenpohja,

Piatkowski,

Tanguy

et al. 2024

EJNMMI radiopharm. chem.

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Background Positron emission tomography is widely used to study biological processes without disrupting normal physiological functions. Traditional radiotracer synthesis and industrial market is focused on producing large batches of 18 F-labelled tracers, especially [ 18 F]FDG. Accessibility to smaller quantity of diverse radiopharmaceuticals is a key to enable a more personalised approach in nuclear medicine. A novel microfluidic module, iMiDEV™, has earlier been shown to be a versatile labelling platform as it has been used in the production of Na[ 18 F]F and various 11 C- and 68 Ga-labelled tracers. In the current study our aim was to utilise iMiDEV™ in the synthesis of fluorine-18-labelled radiotracers, specifically [ 18 F]DPA-714, [ 18 F]LBT-999 and [ 18 F]fallypride. Results [ 18 F]DPA-714, [ 18 F]LBT-999 and [ 18 F]fallypride have been produced in up to 24%, 12% and 11% radiochemical yield, respectively, using the microfluidics based iMiDEV™ labelling platform. Activity yields at the end of synthesis were 3.6 GBq, 2.1 GBq and 2.3 GBq, respectively. All individual synthesis steps were studied for efficient activity transfer and labelling and the optimised synthesis sequence was fully automated. Conclusion In this paper, we have demonstrated fully automated production of different 18 F-tracers of clinical relevance with moderate to good yields using microfluidic iMiDEV™ platform. Our work is a step towards more personalised, dose-on-demand manufacturing of PET radiopharmaceuticals. Supplementary Information The online version contains supplementary material available at 10.1186/s41181-024-00315-6.

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Microfluidic synthesis of radiotracers: recent developments and commercialization prospects

Abstract: Current radiotracer production approaches restrict clinicians' access to a wide range of targeted probes. In this review, we assess the current state of microfluidic synthesis platforms with a view towards future dose-on-demand production.

Cited by 4 publications

References 146 publications

Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline

Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Production of [18F]DPA-714, [18F]fallypride and [18F]LBT-999 using iMiDEV, a fully automated microfluidic platform: towards clinical radiopharmaceutical production

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