Modified automated synthesis of sodium 2-[18F]fluoroacetate using a TracerlabFXN synthesizer.


Modified automated synthesis of sodium 2-[18F]fluoroacetate using a TracerlabFXN synthesizer.

Kniess, T.; Richter, S.; Steinbach, J.

1. Introduction:

Prostate cancer is the most frequently diagnosed cancer in men over the age of 40 years in Europe and the USA and its early detection is crucial for prognosis and outcome of the disease. Besides the established radiotracers based on 11C- and 18F-labeled choline [11C]acetate is used for the early detection of prostate cancer and its recurrence. 2-[18F]Fluoroacetate has been proposed as alternative to [11C]acetate offering the advantage of longer half-life which facilitates synthesis, shipping and allowing longer imaging protocols. A few radiosyntheses of the radiotracer have been published in the past, mainly based on trapping of the 2-[18F]fluoroacetate ethylester on C18 cartridges (Oasis HLB), followed by acidic hydrolysis [1-3]. Our approach is the fully automated synthesis of 2-[18F]fluoroacetate with a TracerlabFXN synthesizer including separation of the radiotracer via anion exchange cartridges in alkaline solution.

2. Materials and methods:

The radiolabeling with [18F]fluoride was performed with 2-methanesulfonyl-acetic acid t-butyl-ester as precursor in acetonitrile at 100°C. After hydrolysis with 1M HCl and addition of 1M NaOH the alkaline reaction mixture was diluted with 20mL of water and passed through a combination of two anion exchange cartridges where 2-[18F]fluoroacetate was trapped. The 2-[18F]fluoroacetate was recovered by elution with NaHCO3 and excess [18F]fluoride was removed by alumina N cartridges to provide radiochemical pure sodium 2-[18F]fluoroacetate (radio-TLC, RP18, acetonitrile/water=85/15; Rf=0.59).

3. Results:

The radiosynthesis of sodium 2-[18F]fluoroacetate was accomplished with a TracerlabFXN synthesizer by a fully automated procedure. The purification of the product was performed by anion exchange cartridges and gave the radiotracer in 27-30% yield (decay-corrected) and 99% radiochemical purity within 30 min total synthesis time.

4. Discussion/Conclusion:

The modified approach of radiosynthesis and purification delivers sodium 2-[18F]fluoroacetate in high radiochemical purity and good radiochemical yield. The improved radio-TLC method using RP18 plates represents an easy system to distinguish [18F]fluoride from 2-[18F]fluoroacetate. Further optimization of this new method utilising a new precursor and a modified separation system is in progress. The conformation of the process to GMP requirements will be performed in the near future.

References:

[1] Sun LQ, Mori T, Dence CS, Ponde DE, Welch MJ, Furukawa T, Yonekura Y, Fujibayashi Y, [2006], Nucl.Med.Biol., 33:153-158
[2] Ponde DE, Dence CS, Oyama N, Kim J, Tai YC, Laforest R, Siegel BA, Welch MJ, [2007], J.Nucl.Med., 48(3): 420-428
[3] Marik J, Ogasawara A, McNulty BM, Ross J, Flores JE, Gill HS, Tinianow JN, Vanderbilt AN, Nishimura M, Peale F, Pastuskovas C, Greve JM, van Bruggen N, Williams SP, [2009], J.Nucl.Med., 50(6): 982-990

  • Poster
    15th European Symposium on Radiopharmacy and Radiopharmaceuticals (ESRR), 08.-11.04.2010, Edinburgh, Großbritannien
  • Abstract in refereed journal
    Quarterly Journal of Nuclear Medicine and Molecular Imaging 54(2010)S1, 54

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Publ.-Id: 13996