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ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 12 - 2024 |
doi: 10.3389/fchem.2024.1411312
Development of a Versatile [ 68 Ga]Ga-FAPI-46 Automated Synthesis Suitable to Multi-Elutions of germanium-68/gallium-68 Generators
Provisionally accepted- 1 Radiopharmacologie, Institut Curie, Saint-Cloud, France
- 2 Trasis, Ans, Belgium
- 3 Translational Imaging in Oncology laboratory, Institut Curie, Orsay, Île-de-France, France
- 4 Sofie iTheranostics, Dulles, United States
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.
Keywords: PET, FAPI radiopharmaceuticals, Radiosynthesis, Automation, Prepurification, Gallium-68
Received: 02 Apr 2024; Accepted: 11 Jun 2024.
Copyright: © 2024 Paty, Degueldre, Provost, Schmitt, Trump, Fouque, Vriamont, Valla, Gendron and Madar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Julien Fouque, Radiopharmacologie, Institut Curie, Saint-Cloud, France
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Simon Degueldre
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