Automated production of [18F]FTHA according to GMP

N Savisto, T Viljanen, E Kokkomaki, J Bergman, Olof Solin

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    8 Citations (Scopus)

    Abstract

    14-(R,S)-[F-18]fluoro-6-thia-heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in-house for multistep nucleophilic F-18-fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14-(R,S)-[F-18]fluoro-6-thia-heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer-ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14-(R,S)-[F-18]fluoro-6-thia-heptadecanoic acid, decay-corrected to the end of bombardment, was 13%+/- 6.3%. The total amount of formulated end product was 1.7 +/- 0.8GBq at end of synthesis.
    Original languageUndefined/Unknown
    Pages (from-to)84–93
    Number of pages10
    JournalJournal of Labelled Compounds and Radiopharmaceuticals
    Volume61
    Issue number2
    DOIs
    Publication statusPublished - 2018
    MoE publication typeA1 Journal article-refereed

    Keywords

    • [F-18]FTHA
    • F-18-fluoride
    • process validation
    • radiosynthesis
    • Fatty acid metabolism
    • Automation

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