An Improved Automated Synthesis of [¹⁸F]FIAU on a GE FX-N Pro Module

Objectives: [¹⁸F]1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil, [¹⁸F]FIAU, is a potential PET imaging probe for HSV1-tk gene expression. Our goal is to improve the radiosynthesis of [¹⁸F]FIAU and develop fully automated synthesis on GE FX-N module to allow efficient and reliable production of this tracer.

Methods: Automated synthesis of [¹⁸F]FIAU was performed via a one pot, three-step process. Briefly, to the dried [¹⁸F]tetrabutylammonium fluoride, [¹⁸F]TBAF, in reactor 1 (Figure 1) was added a solution of the triflate sugar precursor and heated at 100 °C for 10 min. To the resulting mixture was added freshly synthesized 5-iodo-2,4-bis((trimethylsilyl)oxy)pyrimidine. The mixture was heated at 100 °C for 15 min. Upon completion, sodium methoxide was added followed by heating at 70 °C for 5 min. The volatile was removed under N₂ flow and vacuum. The crude product was diluted with a solution of HCl (0.6 M) / EtOH and purified by reverse-phase HPLC (10% EtOH in 50 mM H₃PO₄). The product fraction was passed through a 0.22 µm sterile filter and collected in the product vial. The pH of the solution was adjusted to 6-7 with sodium phosphate solution.

Results: The coupling of the sugar to the pyrimidine, a crucial step of the synthesis, was optimized in our approach. The best conversion was achieved under 100 °C for 15 min. No microwave irradiation is necessary which was easily transferred to the GE FX-N module. [¹⁸F]FIAU was produced in an improved RCY of 10-15% (uncorrected, n = 5) in 100 ± 3 min synthesis time. The radiochemical purity was >98% with a specific activity of 1000 - 2000 Ci/mmol (EOS, n = 5).

Conclusion: Sterile dose of [¹⁸F]FIAU can be produced on a GE FX-N Pro module with improved radiochemical yield and good purity. This process is highly reproducible for routine production. Research Support:

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