A new general approach for the rapid access to 2'-deoxy-2'-arabino-[18F]fluoro-5-substituted uridines is presented. Radiolabeled analogs of nucleosides have wide applications as Positron Emission Tomography (PET) tracers for imaging of cell proliferation and immune system organs. However, the problem of quite long syntheses and low radio-corrected yields has hampered their clinical use. In order to overcome this hurdle, a number of technical advances such as on-chip synthesis and robotic devices have been developed, but they all suffer from a significant loss of radioactivity due to short half-life of the 18F atom, namely110 minutes. Herein, we report a distinctly different route for accessing such PET probes. The high yielding fluorination under standard fluorination conditions was carried out in only 40 min starting from the precursor bearing the nuclear base in the a-anomeric position. The anomerisation of the base to the desired b-anomer was governed by its higher thermodynamic stability and achieved with TMSOTf in only 30 min. The subsequent global deprotection was complete in 10 min using TFA mediated hydrolysis. The first step required filtration through an alumina cartridge, while the second and third steps were better done in one pot with a single final purification through a silica gel cartridge. All manipulations can be finished in 110-120 min. Thus a new cold synthesis of FMAU has been successfully conducted. This approach is superior compared to other commonly used methods in terms of time and efficiency of radiolabeling.

General methodology for the radiosynthesis of FMAU and analogous positron emission tomography (PET) probes

248th National Meeting (2014)

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