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

Mattia Asti, Daniela Farioli, Michele Iori, Claudio Guidotti, Annibale Versari, Diana Salvo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalNuclear Medicine and Biology
Volume37
Issue number3
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Quality Control
Choline
Fluorides
Deanol
Ethane
Automation
Thin Layer Chromatography
Radio
Brain Neoplasms
Gas Chromatography
fluoroethylcholine
Prostate
Phospholipids
High Pressure Liquid Chromatography
Membranes
Neoplasms

Keywords

  • 2-[F]fluoroethylcholine
  • FECH
  • Brain cancer
  • One-step reaction
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Efficient automated one-step synthesis of 2-[18F]fluoroethylcholine for clinical imaging : Optimized reaction conditions and improved quality controls of different synthetic approaches. / Asti, Mattia; Farioli, Daniela; Iori, Michele; Guidotti, Claudio; Versari, Annibale; Salvo, Diana.

In: Nuclear Medicine and Biology, Vol. 37, No. 3, 04.2010, p. 309-315.

Research output: Contribution to journalArticle

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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.",
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AB - [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.

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