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. 2022 Feb 1;27(3):994.
doi: 10.3390/molecules27030994.

Fully Automated Macro- and Microfluidic Production of [68Ga]Ga-Citrate on mAIO® and iMiDEVTM Modules

Olga Ovdiichuk  1 , Emilie Roeder  1 , Sébastien Billotte  1 , Nicolas Veran  2 , Charlotte Collet  1   3
Affiliations

Fully Automated Macro- and Microfluidic Production of [68Ga]Ga-Citrate on mAIO® and iMiDEVTM Modules

Olga Ovdiichuk et al. Molecules. .

Abstract

68Ga-radionuclide has gained importance due to its availability via 68Ge/68Ga generator or cyclotron production, therefore increasing the number of 68Ga-based PET radiopharmaceuticals available in clinical practice. [68Ga]Ga-citrate PET has been shown to be prominent for detection of inflammation/infection of the musculoskeletal, gastrointestinal, respiratory, and cardiovascular systems. Automation and comparison between conventional and microfluidic production of [68Ga]Ga-citrate was performed using miniAllInOne® (Trasis) and iMiDEV™ (PMB-Alcen) synthetic modules. Fully automated procedures were elaborated for cGMP production of tracer. In order to facilitate the tracer approval as a radiopharmaceutical for clinical use, a new method for radiochemical identity determination by HPLC analysis to complement standard TLC radiochemical purity measurement was developed. The results showed higher radiochemical yields when using MCX cartridge on the conventional module mAIO®, while a PS-H+ cation exchanger was shown to be preferred for integration into the microfluidic cassette of iMiDEV™ module. In this study, the fully automated radiosynthesis of [68Ga]Ga-citrate using different synthesizers demonstrated reliable and reproducible radiochemical yields. In order to demonstrate the applicability of [68Ga]Ga-citrate, in vitro and in vivo studies were performed showing similar characteristics of the tracer obtained using macro- and microfluidic ways of production.

Keywords: [68Ga]Ga-citrate; automated radiosynthesis; quality control; radiopharmaceuticals.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
[68Ga]Ga-citrate radiosynthesis strategy.
Figure 2
Figure 2
Graphical representation of radiosynthesis of [68Ga]Ga-citrate on mAIO® module.
Figure 3
Figure 3
Schematic representation of iMiDEV™ microfluidic cassette used for [68Ga]Ga-citrate production; highlighted in red—single synthesis on R1 with Vials A and B; highlighted in blue—single synthesis on R3 with vials C and G.
Figure 4
Figure 4
Cerenkov imaging of the residual activity distribution on the cassette after single production of [68Ga]Ga-citrate on R1 chamber with PS-H+ beads; (a) Cerenkov image after synthesis; (b) white-light image of the top of the cassette; (c) merged Cerenkov and white-light images after completion of the synthesis.
Figure 5
Figure 5
HPLC chromatograms of [68Ga]Ga-citrate production. (Top) radioactive detection; (Bottom) UV 215 nm detection.
Figure 6
Figure 6
Dynamic µPET imaging of [68Ga]Ga-citrate up to 120 min post injection (coronal slice; injected dose: 26.7 ± 0.5 MBq; scan duration: 5 frames of 2 min and 22 frames of 5 min); (a) PET image and time activity curve (TAC) of [68Ga]Ga-citrate synthesized on mAIO®; (b) PET image and TAC of [68Ga]Ga-citrate synthesized on iMiDEV™. B: bone; H: heart; LK: left kidney; RK: right kidney; Bl: bladder.
Figure 7
Figure 7
Workflow for automated [68Ga]Ga-citrate production using miniAIO® and iMiDEV™ modules. (A) Overview of main steps of [68Ga]Ga-citrate production. (B) Card panels represent basic processes needed to achieve each of main steps of production.
See this image and copyright information in PMC

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