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        <Affiliation>Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
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      <JournalTitle>Acta Medica Okayama</JournalTitle>
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        <Year>2026</Year>
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        <FirstName EmptyYN="N">Shigetomo</FirstName>
        <LastName>TSUJI</LastName>
        <Affiliation>Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
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      <JournalTitle>Acta Medica Okayama</JournalTitle>
      <Issn>1999-4923</Issn>
      <Volume>18</Volume>
      <Issue>1</Issue>
      <PubDate PubStatus="ppublish">
        <Year>2026</Year>
        <Month/>
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    <ArticleTitle>Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use</ArticleTitle>
    <FirstPage LZero="delete">123</FirstPage>
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        <FirstName EmptyYN="N">Xinyu</FirstName>
        <LastName>Chen</LastName>
        <Affiliation>Nuclear Medicine, Faculty of Medicine, University of Augsburg</Affiliation>
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      <Author>
        <FirstName EmptyYN="N">Kaito</FirstName>
        <LastName>Ohta</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
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      <Author>
        <FirstName EmptyYN="N">Hiroyuki</FirstName>
        <LastName>Kimura</LastName>
        <Affiliation>Agency for Health, Safety and Environment, Kyoto University</Affiliation>
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      <Author>
        <FirstName EmptyYN="N">Yusuke</FirstName>
        <LastName>Yagi</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
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      <Author>
        <FirstName EmptyYN="N">Takanori</FirstName>
        <LastName>Sasaki</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Naoko</FirstName>
        <LastName>Nose</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Masaru</FirstName>
        <LastName>Akehi</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Tomohiko</FirstName>
        <LastName>Yamane</LastName>
        <Affiliation>Department of Molecular Imaging Research, Kobe City Medical Center General Hospital</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Rudolf A.</FirstName>
        <LastName>Werner</LastName>
        <Affiliation>Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich</Affiliation>
      </Author>
      <Author>
        <FirstName EmptyYN="N">Takahiro</FirstName>
        <LastName>Higuchi</LastName>
        <Affiliation>Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University</Affiliation>
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    <Abstract>Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60&#8211;70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 °C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility.</Abstract>
    <CoiStatement>No potential conflict of interest relevant to this article was reported.</CoiStatement>
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      <JournalTitle>Acta Medica Okayama</JournalTitle>
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        <Year>2025</Year>
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        <FirstName EmptyYN="N">Hidenori</FirstName>
        <LastName>TACHIBANA</LastName>
        <Affiliation>Okayama University</Affiliation>
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        <FirstName EmptyYN="N">Kanako</FirstName>
        <LastName>MATSUNAGA</LastName>
        <Affiliation>Okayama University</Affiliation>
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        <Affiliation>Graduate School of Natural Science and Technology, Okayama university</Affiliation>
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        <Affiliation>Graduate School of Natural Science and Technology, Okayama university</Affiliation>
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