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. 2022 Dec 13;27(24):8843.
doi: 10.3390/molecules27248843.

Production of [11C]Carbon Labelled Flumazenil and L-Deprenyl Using the iMiDEV™ Automated Microfluidic Radiosynthesizer

Hemantha Mallapura  1 , Laurent Tanguy  2 , Bengt Långström  3 , Ludovic Le Meunier  2 , Christer Halldin  1 , Sangram Nag  1
Affiliations

Production of [11C]Carbon Labelled Flumazenil and L-Deprenyl Using the iMiDEV™ Automated Microfluidic Radiosynthesizer

Hemantha Mallapura et al. Molecules. .

Abstract

In the last decade, microfluidic techniques have been explored in radiochemistry, and some of them have been implemented in preclinical production. However, these are not suitable and reliable for preparing different types of radiotracers or dose-on-demand production. A fully automated iMiDEV™ microfluidic radiosynthesizer has been introduced and this study is aimed at using of the iMiDEV™ radiosynthesizer with a microfluidic cassette to produce [11C]flumazenil and [11C]L-deprenyl. These two are known PET radioligands for benzodiazepine receptors and monoamine oxidase-B (MAO-B), respectively. Methods were successfully developed to produce [11C]flumazenil and [11C]L-deprenyl using [11C]methyl iodide and [11C]methyl triflate, respectively. The final products 1644 ± 504 MBq (n = 7) and 533 ± 20 MBq (n = 3) of [11C]flumazenil and [11C]L-deprenyl were produced with radiochemical purities were over 98% and the molar activity for [11C]flumazenil and [11C]L-deprenyl was 1912 ± 552 GBq/µmol, and 1463 ± 439 GBq/µmol, respectively, at the end of synthesis. All the QC tests complied with the European Pharmacopeia. Different parameters, such as solvents, bases, methylating agents, precursor concentration, and different batches of cassettes, were explored to increase the radiochemical yield. Synthesis methods were developed using 3-5 times less precursor than conventional methods. The fully automated iMiDEV™ microfluidic radiosynthesizer was successfully applied to prepare [11C]flumazenil and [11C]L-deprenyl.

Keywords: PET radiotracers; [11C]L-deprenyl; [11C]flumazenil; dose-on-demand (DOD); iMiDEV™; microfluidic cassette; microfluidics; radiosynthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 5
Figure 5
Precursor loading on the R1 from the vial E and other reagents placed on the respective positions.
Figure 1
Figure 1
iMiDEV™ automated microfluidic radiosynthesizer.
Figure 2
Figure 2
The detailed view of iMiDEV™ supervision software view (HMI).
Figure 3
Figure 3
iMiDEV™ microfluidic cassette: Reactors (R1–R3 for reaction and R4 for SPE purification) and vial’s positions (A to F for 4 mL vials and G to I for 15 mL vials).
Figure 4
Figure 4
Reaction schematic for [11C]flumazenil and [11C]L-deprenyl synthesis.
Figure 6
Figure 6
Recorded radioactivity data from R1, R2, R3 and R4 reactors from radio detectors during the complete radiosynthesis.
See this image and copyright information in PMC

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