One-pot and one-step automated radio-synthesis of [18F]AlF-FAPI-74 using a multi purpose synthesizer: a proof-of-concept experiment

• Published in: EJNMMI radiopharmacy and chemistry Vol. 6; no. 1; p. 28
• Main Authors: Naka, Sadahiro, Watabe, Tadashi, Lindner, Thomas, Cardinale, Jens, Kurimoto, Kenta, Moore, Melissa, Tatsumi, Mitsuaki, Mori, Yuriko, Shimosegawa, Eku, Valla, Frank, Kato, Hiroki, Giesel, Frederik L.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 21.08.2021; Springer Nature B.V; SpringerOpen
• Subjects: [18F]AlF-FAPI-74; Aluminum; Aluminum chloride; Anion exchanging; Ascorbic acid; Automated synthesis; Automation; Bioaccumulation; Buffers; Cartridges; Eluents; Elution; Ethanol; Fibroblast activation protein; Fluorides; Fluorination; Imaging; Impurities; Medicine; Medicine & Public Health; Methodology; Molecular Medicine; Nuclear Chemistry; Nuclear Medicine; pH effects; Pharmacotherapy; Positron emission; Positron emission tomography; Purity; Radioactivity; Radiochemistry; Radiology; Recovery; Room temperature; Selectivity; Stroma; Synthesis; Tumors; F]AlF-FAPI-74; [; Positron emission tomography; Fibroblast activation protein; Automated synthesis
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-021-00142-z

Background Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [ 18 F]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, [ 18 F]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 [ 18 F]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [ 18 F]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [ 18 F]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [ 18 F]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [ 18 F]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 [ 18 F]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 [ 18 F]AlF-FAPI-74 was 11.3 ± 1.1 GBq at the end of synthesis from 32 to 40 GBq of [ 18 F]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. 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.