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PET imaging of central σ 1 receptors: Automated synthesis and purification of [18F]fluspidine

Maisonial, A.; Funke, U.; Fischer, S.; Hiller, A.; Wünsch, B.; Steinbach, J.; Brust, P.

Objectives: Sigma1 (σ1) receptors represent attractive targets for the development of new therapeutic drugs and diagnostic imaging agents for various cerebral diseases. Currently, there is a growing interest in the development of selective and high affinity radioligands for in vivo imaging studies of these receptors using positron emission tomography (PET). With this view, we recently developed a promising fluorinated radioligand, [18F]fluspidine, which offers great potential for neuroimaging of central σ1 receptors with PET [1,2]. Herein we report on a first reliable and high yield automatic synthesis of [18F]fluspidine.
Methods: The synthesis of [18F]fluspidine was performed in a lead-shielded hot cell using a modified TRACERlab FXFN synthesizer. The synthesis module is schematized in Figure 1. First, target water solution was passed through a preconditioned anion exchange cartridge (1). Trapped [18F]fluoride was then eluted to the reactor (2) with a potassium carbonate solution (3). A solution of K2.2.2 in acetonitrile (4) was added and the mixture was dried azeotropically according to standard procedures. The K[18F]F-K2.2.2-carbonate complex reacted with the corresponding tosylate precursor in acetonitrile (5) at 85°C for 15 minutes. After cooling, the crude reaction mixture was diluted with water (6) and directly applied to an isocratic semi-preparative RP-HPLC for purification (7), featured by three optional systems of mobile (organic solvent/H2O with no, neutral or acidic buffer) and stationary phase (nonpolar and polar encapped RP). The appropriate fraction was collected in a flask prefilled with water (8) and the whole solution was passed through a solid phase extraction cartridge (9). The trapped radiotracer was then washed with water (10) and finally eluted to the product vial (11) with absolute ethanol (12).

Results: Nucleophilic radiofluorination of the tosylate precursor was optimized regarding reaction time, temperature and concentration to reach labelling efficiencies > 87%. After purification by semi-preparative HPLC and solid phase extraction methods, [18F]fluspidine was produced within 60-75 minutes for the entire process with an overall radiochemical yield of 37.9 ± 3.9% (based on cyclotron-produced [18F]fluoride ion). The radiochemical purity exceeded 99 % in all cases and the specific activity determined at the end of the process was > 120 GBq/µmol.
Conclusions: A rapid one-pot automated procedure for the regular and consistent production of [18F]fluspidine was successfully accomplished with highly reproducible yields as well as high radiochemical purity and specific activity. The implementation of this radiosynthesis into a commercial platform will make [18F]fluspidine easier accessible for further preclinical and clinical studies.
Research Support: This work was supported by the Deutsche Forschungsgemeinschaft.
References: [1] Große Maestrup, E. et al. (2011), Bioorg. Med. Chem., 19, 393-405, [2] Fischer, S. et al. (2011), Eur. J. Nucl. Med. Mol. Imaging., 38, 540-551.

  • Poster
    ISRS2011, 28.08.-02.09.2011, Amsterdam, The Netherlands
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 54(2011)1, 420-420
    ISSN: 0362-4803

Publ.-Id: 15713