One-Pot And One-Step Automated Radio-Synthesis Of [F-18]Alf-Fapi-74 Using A Multi Purpose Synthesizer: A Proof-Of-Concept Experiment

Background Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [F-18]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [F-18]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer. Herein, we report a one-pot and one-step automated radiosynthesis method using a multi purpose synthesizer. Results Radiosynthesis of [F-18]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [F-18]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [F-18]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [F-18]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [F-18]fluoride with only 300 mu L of eluent ranged 90 +/- 9% by introduction from the male side and elution from the female side of the cartridge. In automated synthesis, the eluted [F-18]fluoride and precursor solution containing aluminum chloride were mixed; then, fluorination was performed in a one-pot and one-step process at room temperature for 5 min, followed by 15 min at 95 degrees C. As a result, the radioactivity of [F-18]AlF-FAPI-74 was 11.3 +/- 1.1 GBq at the end of synthesis from 32 to 40 GBq of [F-18]fluoride, and its radiochemical yield was 37 +/- 4% (n = 10). The radiochemical purity at the end of the synthesis was >= 97% for all formulation solutions. When the diluent was saline, the radiochemical purity markedly decreased after 4 h of synthesis. In contrast, with phosphate-buffered saline (pH 7.4) or 10 mM phosphate-buffered saline (pH 6.7) containing 100 mg of sodium ascorbate, the radiochemical purity was stable at 97%. Non-radioactive AlF-FAPI-74 and total impurities, including non-radioactive AlF-FAPI-74, were 0.3 +/- 0.1 mu g/mL and 2.8 +/- 0.6 mu g/mL. Ethanol concentration and residual DMSO were 5.5 +/- 0.2% and 21 +/- 6 ppm, respectively. Conclusions We established a one-pot one-step automated synthesis method using a CFN-MPS200 synthesizer that provided high radioactivity and stable radiochemical purity for possible clinical applications.