An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use

[⁶⁸Ga]Ga-FAPI-46 is a promising new tracer for the imaging of fibroblast activation protein (FAP) by positron emission tomography (PET). Labeled FAP inhibitors (FAPIs) have demonstrated uptake in various types of cancers, including breast, lung, prostate, pancreatic and colorectal cancer. FAPI-PET also possesses a practical advantage over FDG-PET as fasting and resting are not required. [⁶⁸Ga]Ga-FAPI-46 exhibits enhanced pharmacokinetic properties, improved tumor retention, and higher contrast images than the earlier presented [⁶⁸Ga]Ga-FAPI-02 and [⁶⁸Ga]Ga-FAPI-04. Although a manual synthesis protocol for [⁶⁸Ga]Ga-FAPI-46 was initially described, in recent years, automated methods using different commercial synthesizers have been reported. In this work, we describe the development of the automated synthesis of [⁶⁸Ga]Ga-FAPI-46 using the iPHASE MultiSyn synthesizer for clinical applications. Initially, optimization of the reaction time and comparison of the performance of four different solid phase extraction (SPE) cartridges for final product purification were investigated. Then, the development and validation of the production of 0.6-1.7 GBq of [⁶⁸Ga]Ga-FAPI-46 were conducted using these optimized parameters. The product was synthesized in 89.8 ± 4.8% decay corrected yield (n = 6) over 25 min. The final product met all recommended quality control specifications and was stable up to 3 h post synthesis.