Quick Automatic Synthesis of Solvent-Free 16α-[F] Fluoroestradiol: Comparison of Kryptofix 222 and Tetrabutylammonium Bicarbonate.

Estrogen receptor (ER) expression level of human breast cancer often reflects the stage of disease and is usually monitored by immunohistochemical staining . The preferable non-invasive and real-time diagnosis is more accessible by PET scan using 16α-[F]FES. The objective of this study was to develop a quick automatic method for synthesis of solvent-free 16α-[F]FES using a CFN-MPS-200 synthesis system and compare the catalytic efficiency of two phase transfer catalysts, Kryptofix 222/KCO (K222/KCO) and tetrabutylammonium hydrogen carbonate (TBA·HCO). In this method, phase transfer catalysts K222/KCO and TBA·HCO were used, respectively. The intermediate products were both hydrolyzed with hydrochloric acid and neutralized with sodium bicarbonate. The crude product was purified with semi-preparative HPLC, and the solvent was removed by rotary evaporation. The effects of radiofluorination temperature and time on the synthesis were also investigated. Radiochemical purity of solvent-free product was above 99% and the decay-corrected radiochemical yield of 16α-[F]FES was obtained in 48.7 ± 0.95% (catalyzed by K222/KCO, = 4) and 46.7 ± 0.77% (catalyzed by TBA·HCO, = 4, respectively). The solvent-free 16α-[F]FES was studied in clinically diagnosed breast cancer patients, and FES-PET results were compared with pathology diagnosis results to validate the diagnosis value of 16α-[F]FES. The new method was more reliable, efficient, and time-saving. There was no significant difference in catalytic activity between K222/KCO and TBA·HCO.