Development of a Synthetic Method for [⁶⁸Ga]Ga-FAPI-04 Using a Cassette-based Synthesizer

Ga]Ga-FAPI-04 is a promising radiopharmaceutical that binds specifically to fibroblast activation protein, which is overexpressed in more than 90% of malignant epithelial tumors but not in normal healthy tissue.This study aimed to develop an efficient method for producing 68 Ga-labelled FAPI-04 using a cassette-based automated synthesizer.[ 68 Ga]GaCl3 was eluted from an Eckert & Ziegler Medical germanium-68/gallium-68 generator using 2.5 mL of 0.1 M HCl.The synthesis of the [ 68 Ga]Ga-FAPI-04 was performed using different concentrations of HEPES (1∼2.5 M; 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) in 3∼10 minutes; amounts of FAPI-04 precursor (5∼50 μg) and reaction temperature (25℃∼100℃) were optimized on the BIKBox Ⓡ synthesizer.The labeling efficiency of [ 68 Ga]Ga-FAPI-04 was greater than 96% (decay corrected) using 25 μg FAPI-04 synthesized in 10 minutes at 100°C in 2 M HEPES (pH 3.85), and its stability was greater than 99% at 6 hours.The total synthesis time of [ 68 Ga]Ga-FAPI-04 was 32.4 minutes, and the product met all quality control criteria.In this study, we developed and optimized a labeling method using [ 68 Ga]Ga-FAPI-04 using a cassette-based synthesizer.The devised method is expected to be useful for supplying [ 68 Ga]Ga-FAPI-04 for diagnosis in clinical practice.