[Implementation of ⁶⁸Ga-FAPI-46 labelling as part of the PRECISION clinical trial]

Triple-negative breast cancer is a subtype of breast cancer for which [18F]FDG PET imaging has limitations. Fibroblast activation protein, which is overexpressed in the tumor microenvironment, is a promising target for imaging these cancers. This study is part of the PRECISION clinical trial, promoted by the Centre Henri-Becquerel, which aims to evaluate whether [68Ga]Ga-FAPI-46 PET imaging can predict the oncological response to neoadjuvant chemo-immunotherapy. As [68Ga]Ga-FAPI-46 is an experimental drug without marketing authorization in France, its production requires regulatory approval from the French National Agency for Medicines and Health Products Safety (ANSM) via the submission of a Common Technical Document (CTD). The radiosynthesis of [68Ga]Ga-FAPI-46 was performed using a Trasis Mini AIO automated system. [68Ga]GaCl3 was obtained by elution from a GalliaPharm generator. Labeling was performed by heating the FAPI-46 precursor with [68Ga]GaCl3 at 95°C for 10minutes, followed by purification by solid-phase extraction and terminal sterilizing filtration. Validation of the method required seven syntheses, including the establishment of rigorous quality controls in accordance with the European Pharmacopoeia. The main controls performed were: radiochemical purity by HPLC and TLC, identification of [68Ga]Ga, stability by forced degradation at 35°C, microbiological tests (sterility, bacterial endotoxins), organoleptic characteristics, and pH. The analytical methods demonstrated compliance with the validation criteria for frontal ratio, precision, robustness, and linearity. The three validation batches required for the CTD met all release criteria, confirming the reliability of the method. The automated synthesis method for [68Ga]Ga-FAPI-46 using the Mini-AIO automated system and the Eckert generator was successfully validated. The analytical and quality control data will subsequently enable the CTD to be submitted to the ANSM, allowing the experimental radiopharmaceutical to be used in the PRECISION clinical trial.