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Background <p>We previously reported the first-in-human evaluation of 3-[<sup>18</sup>F]-fluoro-2,2-dimethylpropionic acid ([<sup>18</sup>F]FPIA) for imaging aberrant lipid metabolism and cancer detection. The first-generation semi-automated radiosynthesis of [<sup>18</sup>F]FPIA required HPLC purification to provide injection solution devoid of precursor (methyl 2,2-dimethyl-3-[(4-methylbenzenesulfonyl)oxy]propanoate), radioactive intermediate (methyl-3-([18F]fluoro)-2,2-dimethylpropanoate), and potential chemical impurities (tosic acid, 3-hydroxy-2,2-dimethylpropanoic acid and unlabelled FPIA). In readiness for global use of [<sup>18</sup>F]FPIA, we report a significant improvement to the GMP production through development of a fully-automated solid-phase extraction (SPE) purification method.</p> Results <p>We developed a fully-automated SPE purified radiosynthesis on FASTLab™ for GMP readiness that was translated to and validated on the Trasis AIO™ platform for routine clinical use. Purification of the radiotracer by SPE on both systems was achieved (&gt; 98% radiochemical purity), increasing the radiochemical yield compared to the HPLC-based purification method. Non-decay-corrected radiochemical yields (RCY, n.d.c) were 30.3 ± 2.3% (n = 8) and 25.8 ± 6.6% (n = 46) on GE FASTlab™ and Trasis AIO™, respectively. Non-radioactive FPIA and other analytes determined by HPLC were below the limit of detection (&lt; 1.0&#xa0;µg/mL) from GE FASTlab™ and ≤ 1.2&#xa0;µg/mL from Trasis AIO™.</p> Conclusions <p>The synthesis of [<sup>18</sup>F]FPIA was validated on the Trasis AIO™ platform for GMP production and is currently used to produce clinical doses for phase II clinical trials. Readiness for GMP validation was also demonstrated on GE FASTlab™ and can be adopted on other automated platforms.</p>

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An improved fully-automated GMP radiosynthesis of [18F]fluoro-pivalic acid with solid-phase extraction purification

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月21日

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  • Chris Barnes,
  • Frazer Twyman,
  • Ramla O. Awais,
  • Dylan Pritchard,
  • Matthias Glaser,
  • David R. Turton,
  • Diana Brickute,
  • Graham Smith,
  • Erik Årstad,
  • Louis Allott,
  • Eric O. Aboagye

摘要

Background

We previously reported the first-in-human evaluation of 3-[18F]-fluoro-2,2-dimethylpropionic acid ([18F]FPIA) for imaging aberrant lipid metabolism and cancer detection. The first-generation semi-automated radiosynthesis of [18F]FPIA required HPLC purification to provide injection solution devoid of precursor (methyl 2,2-dimethyl-3-[(4-methylbenzenesulfonyl)oxy]propanoate), radioactive intermediate (methyl-3-([18F]fluoro)-2,2-dimethylpropanoate), and potential chemical impurities (tosic acid, 3-hydroxy-2,2-dimethylpropanoic acid and unlabelled FPIA). In readiness for global use of [18F]FPIA, we report a significant improvement to the GMP production through development of a fully-automated solid-phase extraction (SPE) purification method.

Results

We developed a fully-automated SPE purified radiosynthesis on FASTLab™ for GMP readiness that was translated to and validated on the Trasis AIO™ platform for routine clinical use. Purification of the radiotracer by SPE on both systems was achieved (> 98% radiochemical purity), increasing the radiochemical yield compared to the HPLC-based purification method. Non-decay-corrected radiochemical yields (RCY, n.d.c) were 30.3 ± 2.3% (n = 8) and 25.8 ± 6.6% (n = 46) on GE FASTlab™ and Trasis AIO™, respectively. Non-radioactive FPIA and other analytes determined by HPLC were below the limit of detection (< 1.0 µg/mL) from GE FASTlab™ and ≤ 1.2 µg/mL from Trasis AIO™.

Conclusions

The synthesis of [18F]FPIA was validated on the Trasis AIO™ platform for GMP production and is currently used to produce clinical doses for phase II clinical trials. Readiness for GMP validation was also demonstrated on GE FASTlab™ and can be adopted on other automated platforms.