Automatic synthesis of 16α-[ 18F]fluoro-17β-estradiol using a cassette-type [ 18F]fluorodeoxyglucose synthesizer

Abstract

16α-[ 18F]fluoro-17β-estradiol ([ 18F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [ 18F]FES by modifying a cassette-type [ 18F]fluorodeoxyglucose synthesizer. Two milligrams of 3- O-methoxymethyl-16,17- O-sulfuryl-16-epiestriol in acetonitrile was heated at 105°C for 10 min with dried [ 18F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95°C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO 3, and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-μm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [ 18F]FES was synthesized with a yield of 76.4±1.9% ( n=5). The yield as the final product for clinical use was 42.4±3.2% ( n=5, decay corrected). The total preparation time was 88.2±6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/μmol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [ 18F]FES safe for clinical use with high and reproducible yield.