INTRODUCTION

METHODS

RESULTS

[18F]-Fluorocholine is used with PositronEmission Tomography to detect metastaticprostate cancer [1], recurrent brain tumors andhepatocellular carcinoma [2,3]. Automatedmethods to synthesize [18F]-Fluorocholine areavailable on several radiosynthesis platforms,but these approaches suffer from fluctuationsof yield, emission of radioactive gas when usingthe older dibromomethane method and highquantity of 2-Dimethylethanolamine (DMEA) inthe final product. Herein, we present anautomated one-pot method with an improvedpurification for the efficient routine productionof [18F]-Fluorocholine under cGMP conditions,avoiding the pitfalls of the gaseous method.

This synthetic method has been successfullyimplemented on an AllinOne synthesizer andgives a high reproducible yield without release ofany radioactive gas and a high chemical (DMEAcontent < 1 µg/mL) and radiochemical (RCP >99%) purities. Total synthesis time is about 39minutes. Typical non-decay-corrected yields of[18F]-Fluorocholine are around 25 ± 5% non-decaycorrected, whatever the starting activity (Figure2). The product is stable up to 10 hours with avolumic activity of 4,5 GBq/mL and is compliant toany QC testing.

[18F]-Fluorocholine is prepared using anAllinOne synthesizer. The reaction of methylenebis(toluene-4-sulfonate) precursor (1) withcyclotron-produced [18F]Fluoride gives the[18F]Fluoromethyl 4-methylbenzene sulfonateintermediate (2). Upon completion of thelabelling step, a mixture of DMEA and DMF isadded to the reactor and the quaternization ofthe amino group is achieved leading tocompound 3. The solution is efficiently purifiedpassing through a series of SPE Sep-Pak tC18and HLB cartridges and [18F]-Fluorocholine istrapped on Sep-Pak CM cartridges. Afterelimination of residual impurities such as theDMEA, the formulated product (4) is elutedfrom the CM cartridges with 0.9% physiologicalsaline, passed through a 0.22 µm filter to asterile dose vial and submitted for qualitycontrol testing.

A fully automated synthesis of [18F]-Fluorocholine,purification and formulation included, has beenimplemented on the AllinOne synthesizer byTrasis with high reproducible radiochemical yieldand efficient chemical purity.

References:

1. Kotzerke, J., et al., Eur. J. Nuc. Med. 27, 14152. Hara, T., et al., J. Nuc. Med. 36, 9903.Hara, T., et al., J. Nuc. Med. 38, 842

M. Otabashi 1 ; C. Vriamont 1 ; T. Vergote 1 ; C. Desfours 1 ; J-L. Morelle 1 andG. Philippart 1

1 Trasis SA, Liege, Belgium,

High reproducible yield [18F]-FCholine production on AllinOne (Trasis) at commercial scale

CONCLUSIONS

Figure 1. Synthetic pathway of [18F]-Fluorocholine

Figure 2. [18F]-Fluorocholine output (non-decay corrected) versusthe starting activity (user’s data)