Development of an automatized production of 68Ga-FAPI-46 in an Hospital
1 October 2025
A. Pierrot1, K. Casagrande1, J. Costes1, J. Delage1, F. Sadeghipour2,3,41 Radiopharmacy Unit, Department of Pharmacy, Lausanne University Hospital and University of Lausanne, Lausanne, SWITZERLAND,
2 Department of Pharmacy, Lausanne University Hospital and University of Lausanne, Lausanne, SWITZERLAND,
3 Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, SWITZERLAND,
4 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, SWITZERLAND.
Intro
68Ga-FAPI-46 peptides are positron emitters molecules and also Fibroblast Activation Protein (FAP) inhibitors. This promising radiopharmaceutical is being developed with the aim of improving the early detection and the management of FAP overexpressing tumors. Our project was to develop and validate a labeling protocol of this radiopharmaceutical in the aim of setting up clinical trials in our hospital.
Materials and Methods
Using a MiniAiO®(Trasis) synthetizer, the production is made aseptically in a shielded hot cell, under controlled atmosphere. The peptide is mixed with 68Ga, obtained by eluting a 68Ge/68Ga generator (Galliapharm®) with 5 mL of HCl and pH is maintained at 4 thanks to an acetate buffer. Afterwards, an heating step at 95°C for 10 minutes is performed. After the incubation, the solution is purified through a cartridge and then, rinsed with ethanol. Finally, a sterilizing filtration is realized before a dilution step with NaCl 0.9% and ascorbic acid, to obtain a final volume of 10 mL. Regarding quality controls, the assessment of radiochemical purity (RCP) was made by radio-HPCL and by radio-TLC in accordance to European Pharmacopea (Ph.Eur). Microbiological monitoring and sterility assays were made in addition to bubble point test on the sterilizing filter.
Results
Three validation batches were performed and RCP was 99.5% ± 0.2% with HPLC and 99.2% ± 0.1% with TLC. Stability was assessed and validated until 3 hours post-production because of the short shelf-life of 68Ga (RCP 99.3% ± 0.2% with HPLC and 99.1% ± 0.2% with TLC). Residual ethanol content was measured by gas chromatography and the dosage was 7.2% ± 0.0%. All microbiological tests were compliant.
Conclusion
Our project shows that this labelling protocol enables reliable automated synthesis of 68Ga-FAPI-46. The quality criteria given by Ph. Eur are compliant and the radiopharmaceutical drug can be injected to patient safely. These data allow us to consider conducting clinical trials with this drug in our hospital and even a theranostic approach with labelling FAPI-46 with 177Lu, which is already used for therapeutic purposes.