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

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.

Added Value of Scintillating Element in Cerenkov-Induced Photodynamic Therapy

“…The radiosynthesis was realized as previously described [ 45 , 46 ]. Briefly, [ 68 Ga]-citrate was produced using mAIO module (TRASIS) by trapping of 68 Ga-eluate obtained from a 68 Ge/ 68 Ga generator (around 400 MBq) on MCX cartridge and [ 68 Ga]-citrate was eluted by 4 mL of a commercially available citrate solution (ACD formula A) towards a final vial.…”

Synthesis of [68Ga]Ga-PSMA-11 using the iMiDEV™ microfluidic platform

“…68 Ga-trapping on the R1 chamber of the iMiDEV cassette was successfully performed for the first time for [ 68 Ga]Ga-citrate production. 20 Prior to the integration into the cassette, the evaluation of the trapping-release properties using a concentrated NaCl solution containing HCl as an eluent, 25 on 3 different SPE cartridges mainly applied in conventional syntheses was performed. The commercial Chromafix PS-H + , MCX and SCX cation exchange cartridges were selected for off-cassette experiments (Table 3).…”

“…All cartridges showed excellent trapping properties in accordance with our previously reported results. 20 The widely described in the literature Mueller method using concentrated acidified sodium chloride solution for Ga-68 recovery was investigated. 25 The highest recovery using 3 M NaCl acidified with 30% HCl mixture (eluent 1) was found for the Chromafix PS-H + cartridge (Table 2, entry 1 versus entries 3, 6).…”

“…So far, the radiosynthesis of different radiopharmaceuticals like [ 18 F]NaF, [ 68 Ga]Ga-citrate and [ 11 C] carbon labelled Flumazenil and L-deprenyl has been implemented on the microfluidic cassette and iMiDEV™. [19][20][21] Only solid phase chambers R1, R3 and R4 of the cassette have been explored to implement the syntheses. In this proof-of-concept study, we describe an implementation of [ 68 Ga]Ga-PSMA-11 radiosynthesis on the iMiDEV™ synthesizer in order to expand the capacity of the unique microfluidic architecture including a mixer M2 and a liquid phase reactor R2.…”

Microfluidic-based production of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC using the cassette-based iMiDEV™ microfluidic radiosynthesizer

“…The iMiDEV™ batch-type microfluidic radiosynthesizer was investigated for the synthesis of fluorine-18 ( 18 F), carbon-11 ( 11 C), and 68 Ga-radiotracers at room temperature (Ovdiichuk et al 2021 , 2022 ; Mallapura et al 2022 ) as well as at elevated temperature (Ovdiichuk et al 2023 ). The radiolabeling of DOTA chelators with the 68 Ga-radionuclide requires high temperatures (León-Rodríguez and Kovacs 2008 ).…”