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Background <p>(<i>S</i>)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-glutamic acid ([<sup>18</sup>F]FSPG) is a positron emission tomography radiotracer used to image system x<sub>c</sub><sup>−</sup>, an antiporter that is upregulated in several cancers. Not only does imaging system x<sub>c</sub><sup>−</sup> with [<sup>18</sup>F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [<sup>18</sup>F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [<sup>18</sup>F]FSPG on the Trasis AllinOne™, overcoming previous limitations to provide a user-friendly method ready for clinical adoption.</p> Results <p>The optimised method provided [<sup>18</sup>F]FSPG in 33.5 ± 4.9% radiochemical yield in just 35&#xa0;min when starting with 18–25&#xa0;GBq. Importantly, this method could be scaled up to &gt; 100&#xa0;GBq starting activity with only a modest reduction in radiochemical yield, providing [<sup>18</sup>F]FSPG with a molar activity of 372 ± 65&#xa0;GBq/µmol and excellent radiochemical purity (96.8 ± 1.1%). The formulated product was stable when produced with these high starting activities.</p> Conclusions <p>We have developed the first automated synthesis of [<sup>18</sup>F]FSPG on the Trasis AllinOne™. The method produces [<sup>18</sup>F]FSPG with excellent radiochemical purity and in high amounts suitable for large clinical trials and off-site distribution. The method expands the number of synthesis modules capable of producing [<sup>18</sup>F]FSPG and has been carefully designed for cGMP compliance to simplify regulatory approval for clinical production. The methods developed for the purification of high-activity [<sup>18</sup>F]FSPG are transferrable and should aid the development of clinical [<sup>18</sup>F]FSPG productions on other synthesis modules.</p>

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Compact and cGMP-compliant automated synthesis of [18F]FSPG on the Trasis AllinOne™

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月17日

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  • Rizwan Farooq,
  • Thibault Gendron,
  • Richard S. Edwards,
  • Timothy H. Witney

摘要

Background

(S)-4-(3-18F-Fluoropropyl)-ʟ-glutamic acid ([18F]FSPG) is a positron emission tomography radiotracer used to image system xc−, an antiporter that is upregulated in several cancers. Not only does imaging system xc− with [18F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [18F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [18F]FSPG on the Trasis AllinOne™, overcoming previous limitations to provide a user-friendly method ready for clinical adoption.

Results

The optimised method provided [18F]FSPG in 33.5 ± 4.9% radiochemical yield in just 35 min when starting with 18–25 GBq. Importantly, this method could be scaled up to > 100 GBq starting activity with only a modest reduction in radiochemical yield, providing [18F]FSPG with a molar activity of 372 ± 65 GBq/µmol and excellent radiochemical purity (96.8 ± 1.1%). The formulated product was stable when produced with these high starting activities.

Conclusions

We have developed the first automated synthesis of [18F]FSPG on the Trasis AllinOne™. The method produces [18F]FSPG with excellent radiochemical purity and in high amounts suitable for large clinical trials and off-site distribution. The method expands the number of synthesis modules capable of producing [18F]FSPG and has been carefully designed for cGMP compliance to simplify regulatory approval for clinical production. The methods developed for the purification of high-activity [18F]FSPG are transferrable and should aid the development of clinical [18F]FSPG productions on other synthesis modules.