AUTHOR=Paty Louis-Paul , Degueldre Simon , Provost Claire , Schmitt Camille , Trump Laura , Fouque Julien , Vriamont Charles , Valla Frank , Gendron Thibault , Madar Olivier 

TITLE=Development of a versatile [68Ga]Ga-FAPI-46 automated synthesis suitable to multi-elutions of germanium-68/gallium-68 generators

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1411312

DOI=10.3389/fchem.2024.1411312

ISSN=2296-2646

ABSTRACT=Gallium-68 labeled FAPI-46 has recently been proposed as a novel Positron Emission Tomography imaging probe to diagnose and monitor a wide variety of cancers. Promising results from several ongoing clinical trials have led to a soaring demand for this radiotracer. Typical [ 68 Ga]Ga-FAPI-46 labeling protocols do not cope with multiple generator elutions, leaving radiopharmacies unable to scale-up the production and meet the demand. Here we propose a robust and efficient automated radiosynthesis of [ 68 Ga]Ga-FAPI-46 on the Trasis miniAllinOne synthesizer, featuring a prepurification step which allows multiple generator elutions and ensure compatibility with a wide range of gallium-68 generators.Our approach was to optimize the prepurification step by first testing five different cationic cartridge chemistries. Only the strong cationics (SCX) cartridges tested had sufficient affinities for quantitative trapping >99.9%, while the weak cationics did not exceed 50%. Packaging, rinsing or flowing of the selected SCX cartidge were not noticeable, but improvements in fluidics managed to save time. Based on our previous development experience of [ 68 Ga]Ga-FAPI-46, radiolabelling optimization was also carried out at different temperatures during 10 min. At temperatures above 100°C, radiochemical yield (RCY) > 80% were achieved without significantly increasing of chemical impurities (< 5.5 µg.mL -1 ). The optimized sequence was reproducibly conducted with three different brand of wildely used generator (RCY > 88%). Comparison with radiosyntheses carried-out without prepurification steps was also conclusive in terms of RCY, radiochemical yield and chemical purity. Finally, high-activity tests using elutions from three generators were also successful for these parameters. [ 68 Ga]Ga-FAPI-46 was consistently obtained in good radiochemical yields (> 89%, n=3), and the final product quality was compliant with internal specifications based on European Pharmacopeia. This process is suitable for GMP production and allows scaling-up of routine productions, higher throughput and, ultimately, better patient care.