Abstract
BackgroundFibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [18F]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, [18F]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.ResultsRadiosynthesis of [18F]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [18F]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [18F]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [18F]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [18F]fluoride with only 300 µL 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 [18F]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 °C. As a result, the radioactivity of [18F]AlF-FAPI-74 was 11.3 ± 1.1 GBq at the end of synthesis from 32 to 40 GBq of [18F]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 µg/mL and 2.8 ± 0.6 µg/mL. Ethanol concentration and residual DMSO were 5.5 ± 0.2% and 21 ± 6 ppm, respectively.ConclusionsWe 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.
Highlights
Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [18F]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
Among these, [68Ga]FAPI-46 has already established automation using a synthesizer for clinical application; 68Ga used for radio-labeling was supplied by a 68Ge/68Ga generator (Spreckelmeyer et al 2020)
The important points for transferring the procedure optimized by Giesel et al for manual synthesis to the automated synthesizer were: (1) the collection procedure of produced [18F]fluoride into the reactor with a high recovery rate using a small amount of eluent (300 μL), (2) the method of adding a small amount of reagent (4–300 μL) for fluorination and the fluorination procedure simplify, and (3) the composition of the formulation solution to obtain stable radiochemical purity (RCP) at high radioactivity to ensure that sufficient time is available for in-house clinical research (4 h following the synthesis) (Giesel et al 2021)
Summary
Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [18F]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. [18F]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. The important points for transferring the procedure optimized by Giesel et al for manual synthesis to the automated synthesizer were: (1) the collection procedure of produced [18F]fluoride into the reactor with a high recovery rate using a small amount of eluent (300 μL), (2) the method of adding a small amount of reagent (4–300 μL) for fluorination and the fluorination procedure simplify, and (3) the composition of the formulation solution to obtain stable radiochemical purity (RCP) at high radioactivity to ensure that sufficient time is available for in-house clinical research (4 h following the synthesis) (Giesel et al 2021). In 1) of important point, since it has been reported that elution of [18F]fluoride from QMA column is insufficient at an amount of 300 μL (Kersemans et al 2018), we need to select the type of QMA column, the sorbent amount, and the direction of introduction and elution into the column with reference to the back-flush protocol used by other study (Zlatopolskiy et al 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
