Quick Automatic Synthesis of Solvent-Free 16α-[18F] Fluoroestradiol: Comparison of Kryptofix 222 and Tetrabutylammonium Bicarbonate.

ABSTRACT

Estrogen receptor (ER) expression level of human breast cancer often reflects the stage of disease and is usually monitored by immunohistochemical staining in vitro. The preferable non-invasive and real-time diagnosis in vivo is more accessible by PET scan using 16α-[18F]FES. The objective of this study was to develop a quick automatic method for synthesis of solvent-free 16α-[18F]FES using a CFN-MPS-200 synthesis system and compare the catalytic efficiency of two phase transfer catalysts, Kryptofix 222/K2CO3 (K222/K2CO3) and tetrabutylammonium hydrogen carbonate (TBA·HCO3). In this method, phase transfer catalysts K222/K2CO3 and TBA·HCO3 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-[18F]FES was obtained in 48.7 ± 0.95% (catalyzed by K222/K2CO3, n = 4) and 46.7 ± 0.77% (catalyzed by TBA·HCO3, n = 4, respectively). The solvent-free 16α-[18F]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-[18F]FES. The new method was more reliable, efficient, and time-saving. There was no significant difference in catalytic activity between K222/K2CO3 and TBA·HCO3.