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使用完全自动化微流控平台iMiDEV生产[F]DPA - 714、[F]氟哌利多和[F]LBT - 999:迈向临床放射性药物生产。

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

作者信息

Lahdenpohja Salla, Piatkowski Camille, Tanguy Laurent, Kuhnast Bertrand

机构信息

Université Paris Saclay, CEA Inserm, CNRS, BioMaps, Orsay, 91401, France.

PMB-Alcen, Peynier, 13790, France.

出版信息

EJNMMI Radiopharm Chem. 2024 Dec 18;9(1):86. doi: 10.1186/s41181-024-00315-6.

Abstract

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 F-labelled tracers, especially [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[F]F and various C- and  Ga-labelled tracers. In the current study our aim was to utilise iMiDEV™ in the synthesis of fluorine-18-labelled radiotracers, specifically [F]DPA-714, [F]LBT-999 and [F]fallypride.

RESULTS

[F]DPA-714, [F]LBT-999 and [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 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.

摘要

背景

正电子发射断层扫描被广泛用于研究生物过程,而不会干扰正常生理功能。传统的放射性示踪剂合成和工业市场专注于生产大批量的氟标记示踪剂,尤其是[F]FDG。获得少量多样的放射性药物是在核医学中实现更个性化方法的关键。一种新型微流控模块iMiDEV™, earlier已被证明是一个多功能标记平台,因为它已用于生产Na[F]F以及各种碳和镓标记的示踪剂。在本研究中,我们的目标是利用iMiDEV™合成氟-18标记的放射性示踪剂,特别是[F]DPA - 714、[F]LBT - 999和[F]氟哌利多。

结果

使用基于微流控的iMiDEV™标记平台,分别以高达24%、12%和11%的放射化学产率生产了[F]DPA - 714、[F]LBT - 999和[F]氟哌利多。合成结束时的活度产率分别为3.6 GBq、2.1 GBq和2.3 GBq。对所有单个合成步骤进行了研究,以实现高效的活度转移和标记,并且优化的合成序列实现了完全自动化。

结论

在本文中,我们展示了使用微流控iMiDEV™平台以中等到良好的产率全自动生产具有临床相关性的不同氟示踪剂。我们的工作朝着更个性化、按需给药的PET放射性药物制造迈出了一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdc7/11655818/a32dd0d49beb/41181_2024_315_Fig1_HTML.jpg

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