Radiofluorination and reductive amination using a microfluidic device

Authors

  • Kenneth Dahl,

    Corresponding author
    • Karolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Hospital, Stockholm, Sweden
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  • Magnus Schou,

    1. Karolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Hospital, Stockholm, Sweden
    2. AstraZeneca R&D, Innovative Medicines, CNSP iMed, Södertälje, Sweden
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  • Christer Halldin

    1. Karolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Hospital, Stockholm, Sweden
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Kenneth Dahl, Karolinska Institutet, Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Hospital, S-171 76 Stockholm, Sweden.

E-mail: kenneth.dahl@ki.se

Abstract

A commercial microfluidic device (NanoTek, Advion) was used as a synthesis platform for the preparation of fluorine-18 labelled tertiary amines in two consecutive steps. Firstly, the nucleophilic radiofluorination of an aromatic aldehyde and secondly, the reductive amination to produce the corresponding amine. Fluorine-18 labelled [18F]fluorobenzaldehyde ([18F]2) was obtained in an analytical radiochemical yield (rcy) of 93% and a preparative yield of 60% (decay corrected). The produced [18F]2 was applied in two model reactions yielding [18F]5 and [18F]6 in analytical rcy 70 and 75%, respectively. To further test the utility of this methodology, a delta opioid agonist, [18F]8, was also radiolabelled using the same setup in an analytical rcy of 29%.

In a preparative run, 1050 MBq (28.4 mCi) isolated product ([18F]6) was obtained in a 37.5% decay corrected overall rcy calculated from [18F]fluoride. The radiochemical purity of [18F]6 was greater than 99% and the specific radioactivity 298 GBq/µmol (8052 Ci/mmol) at end of synthesis.

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