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

Abstract

Background 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. 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. Results Radiosynthesis 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. 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.

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

“…[ 18 F]FAPI-74 solution was synthesized using CFN-MPS200 (Sumitomo Heavy Industries), according to a previous study (6). [ 18 F]fluoride eluted with 0.5 M sodium acetate buffer and precursor solution (a mixture of dimethyl sulfoxide, 10 mM aluminum chloride, 20% w/v ascorbic acid, and 4 mM FAPI-74 precursor) was mixed and fluorinated for 5 min at room temperature, followed by 15 min at 95 C. [ 18 F]FAPI-74 was purified from the reaction solution using an hydrophilic-lipophilic balance cartridge and ethanol.…”

“…The FAP inhibitor (FAPI) has gained attention as an excellent PET probe that can accurately detect many types of cancer compared with the conventional glucose analog [ 18 F]FDG. 68 Ga-labeled FAPI ([ 68 Ga]FAPI-04 or [ 68 Ga]FAPI-46) and 18 F-labeled FAPI ([ 18 F]FAPI-74) are most commonly available for clinical use (4)(5)(6). Recently, the number of published papers reporting the excellent performance of FAPI PET has increased, and clinical trials are being conducted (NCT05262855 and NCT05641896).…”

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

“…Naka et al. performed a proof-of-concept automated synthesis of [ 18 F] AlF-FAPI-74 with one-pot and one-step by a multi-purpose synthesizer CFN-MPS200; the radioactivity per batch was 11.3 ± 1.1 GBq, and the RCY was 37.0% ± 4.3% ( 30 ).…”

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

“…As the clinical application of FAPI-PET steadily progresses, an efficient and stable supply of 18 F-labeled FAPI is urgently needed. Recently, we developed an automated radiosynthesis method for [ 18 F]AIF-FAPI-74 [20].…”