1
INTRODUCTION METHODS RESULTS [ 18 F]-Fluorocholine is used with Positron Emission Tomography to detect metastatic prostate cancer [1], recurrent brain tumors and hepatocellular carcinoma [2,3]. Automated methods to synthesize [ 18 F]-Fluorocholine are available on several radiosynthesis platforms, but these approaches suffer from fluctuations of yield, emission of radioactive gas when using the older dibromomethane method and high quantity of 2-Dimethylethanolamine (DMEA) in the final product. Herein, we present an automated one-pot method with an improved purification for the efficient routine production of [ 18 F]-Fluorocholine under cGMP conditions, avoiding the pitfalls of the gaseous method. This synthetic method has been successfully implemented on an AllinOne synthesizer and gives a high reproducible yield without release of any radioactive gas and a high chemical (DMEA content < 1 μg/mL) and radiochemical (RCP > 99%) purities. Total synthesis time is about 39 minutes. Typical non-decay-corrected yields of [ 18 F]-Fluorocholine are around 25 ± 5% non-decay corrected, whatever the starting activity (Figure 2). The product is stable up to 10 hours with a volumic activity of 4,5 GBq/mL and is compliant to any QC testing. [ 18 F]-Fluorocholine is prepared using an AllinOne synthesizer. The reaction of methylene bis(toluene-4-sulfonate) precursor (1) with cyclotron-produced [ 18 F]Fluoride gives the [ 18 F]Fluoromethyl 4-methylbenzene sulfonate intermediate (2). Upon completion of the labelling step, a mixture of DMEA and DMF is added to the reactor and the quaternization of the amino group is achieved leading to compound 3. The solution is efficiently purified passing through a series of SPE Sep-Pak tC18 and HLB cartridges and [ 18 F]-Fluorocholine is trapped on Sep-Pak CM cartridges. After elimination of residual impurities such as the DMEA, the formulated product (4) is eluted from the CM cartridges with 0.9% physiological saline, passed through a 0.22 μm filter to a sterile dose vial and submitted for quality control testing. A fully automated synthesis of [ 18 F]-Fluorocholine, purification and formulation included, has been implemented on the AllinOne synthesizer by Trasis with high reproducible radiochemical yield and efficient chemical purity. References: 1. Kotzerke, J., et al., Eur. J. Nuc. Med. 27, 1415 2. Hara, T., et al., J. Nuc. Med. 36, 990 3.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 and G. 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 [ 18 F]-Fluorocholine Figure 2. [ 18 F]-Fluorocholine output (non-decay corrected) versus the starting activity (user’s data)

High reproducible yield [18F]-FCholine production on ... reproducible yield... · INTRODUCTION METHODS RESULTS [18F]-Fluorocholine is used with PositronEmission Tomography to detect

  • Upload
    others

  • View
    17

  • Download
    0

Embed Size (px)

Citation preview

Page 1: High reproducible yield [18F]-FCholine production on ... reproducible yield... · INTRODUCTION METHODS RESULTS [18F]-Fluorocholine is used with PositronEmission Tomography to detect

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)