Efficient automated one-step synthesis of 2-[¹⁸F]fluoroethylcholine for clinical imaging: optimized reaction conditions and improved quality controls of different synthetic approaches

Abstract 

[¹⁸F]-labelled choline analogues, such as 2-[¹⁸F]fluoroethylcholine (¹⁸FECH), have suggested to be a new class of choline derivatives highly useful for the imaging of prostate and brain tumours. In fact, tumour cells with enhanced proliferation rate usually exhibit an improved choline uptake due to the increased membrane phospholipids biosynthesis. The aim of this study was the development of a high yielding synthesis of ¹⁸FECH. The possibility of shortening the synthesis time by reacting all the reagents in a convenient and rapid one-step reaction was specially considered.

Methods

¹⁸FECH was synthesized by reacting [¹⁸F]fluoride with 1,2-bis(tosyloxy)ethane and N,N-dimethylaminoethanol. The synthesis was carried out using both a one- and a two-step reaction in order to compare the two procedures. The effects on the radiochemical yield and purity by using different [¹⁸F]fluoride phase transfer catalysts, reagents amounts and purification methods were assessed. Quality controls on the final products were performed by means of radio-thin-layer chromatography, gas chromatography and high-performance liquid chromatography equipped with conductimetric, ultraviolet and radiometric detectors.

Results

In the optimized experimental conditions, ¹⁸FECH was synthesized with a radiochemical yield of 43±3% and 48±1% (not corrected for decay) when the two-step or the one-step approach were used, respectively. The radiochemical purity was higher than 99% regardless of the different synthetic pathways or purification methods adopted. The main chemical impurity was due to N,N-dimethylmorpholinium. The identity of this impurity in ¹⁸FECH preparations was not previously reported.

Conclusion

An improved two-step and an innovative one-step reaction for synthesizing ¹⁸FECH in a high yield were reported. The adaptation of a multistep synthesis to a single step process, opens further possibilities for simpler and more reliable automations.

Keywords: 2-[¹⁸F]fluoroethylcholine, ¹⁸FECH, Prostate cancer, Brain cancer, One-step reaction