Synthesis of 18F-fluorodeoxyglucose (FDG) using base hydrolysis

Full text: With the increasing demand for FDG in Australia, a faster method of preparation is needed. Most of the existing automated FDG syntheses rely on the time-consuming acid hydrolysis method for removal of the protecting groups on the tetra-acetylated labelled precursor (TA-FDG). Base hydrolysis has been reported as a faster method by several groups using differing conditions. Here we assess the feasibility of using this method with our existing FDG synthesizer modules from IBA and EBCO. We chose NaOH solution as the most convenient base and tested the efficiency of hydrolysis at concentrations of 0.0, 0.2, 0.3, 0.5 and 1 M. The results showed the presence of three peaks only: TA-FDG, FDG and free fluoride. A correlation was found between the base concentration and extent of defluorination. An optimum concentration of 0.2 M gave complete hydrolysis with no defluorination. Base hydrolysis at elevated temperatures (> 70 deg C) for more than 2 min gave a significant amount (5%) of an unidentified additional impurity in the TLC trace which could not be separated from FDG by the standard SepPak purification. This was overcome by reducing the hydrolysis time to I min to avoid overheating. This way we were able to produce pure FDG in less than 35 min with chemical labelling yields of 65-75% (decay-corrected) with 2 ml 0.2 M NaOH. The base was neutralized by passing through a disposable cation exchange cartridge (Alltech, SCX 600 mg, H+ form) to give pH 5-6 with no detectable trace of kryptofix or FDM