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Background <p>Bacterial infections and antimicrobial resistance constitute significant threats to global human health, resulting in millions of fatalities annually. The development of innovative diagnostic agents is essential to facilitate precision medicine approaches in the battle against infectious diseases. Infection imaging using radiolabeled antimicrobial peptides (AMP) has emerged as a promising approach to detect bacterial infections. UBI(29–41), an AMP fragment, exhibits binding to bacterial cell membranes. Conjugated to chelators, UBI(29–41) has been labeled with radiometals such as <sup>99m</sup>Tc or <sup>68</sup>Ga, and proven its ability to differentiate between sterile inflammation and infection with S. aureus by imaging. Due to its physical properties, <sup>18</sup>F is more favorable for PET/CT imaging. As peptide labeling with <sup>18</sup>F is challenging, we here implemented the Al<sup>18</sup>F labeling approach. This study aims to develop an optimized, fully automated, GMP-compliant process for radiolabeling of NOTA-conjugated UBI(29–41) with Al<sup>18</sup>F for PET/CT imaging of infections.</p> Results <p>Optimized reaction conditions led to the establishment of a robust Al<sup>18</sup>Fcomplexation protocol, which was implemented on a SynChrom R&amp;D module. The labeling reaction was carried out in an acidic medium (pH&#xa0;4.0) at 105&#xa0;°C for 15&#xa0;min, followed by a two-step HPLC purification for 20&#xa0;min. Optimization of reagent concentrations enabled an activity yield up to 10 ± 1&#xa0;GBq, with a radiochemical yield of 24.2 ± 0.6% and an apparent molar activity of 45 ± 4&#xa0;GBq/µmol at end of synthesis (EOS) (<i>n</i> = 3). The radiochemical purity was 96.6 ± 0.3% as determined by analytical HPLC, using UV absorption (220&#xa0;nm). Quality control was successfully established using validated analytical procedures.</p> Conclusions <p>The developed GMP-compliant radiolabelling process yields reproducible results with sufficient activities for further translation and investigations of clinical PET/CT imaging using Al[<sup>18</sup>F]F-NOTA-UBI(29–41) in infectious diseases.</p>

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Optimization of a GMP-compliant automated one-pot synthesis of Al[18F]F-NOTA-Ubiquicidin29 − 41 for bacterial infection imaging by PET/CT

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  • 发表日期：

    2025年7月28日

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  • Anna Meyer,
  • Thomas Ziegler,
  • Jutta Moosbauer,
  • Dirk Hellwig,
  • Christian Fischer

摘要

Background

Bacterial infections and antimicrobial resistance constitute significant threats to global human health, resulting in millions of fatalities annually. The development of innovative diagnostic agents is essential to facilitate precision medicine approaches in the battle against infectious diseases. Infection imaging using radiolabeled antimicrobial peptides (AMP) has emerged as a promising approach to detect bacterial infections. UBI(29–41), an AMP fragment, exhibits binding to bacterial cell membranes. Conjugated to chelators, UBI(29–41) has been labeled with radiometals such as 99mTc or 68Ga, and proven its ability to differentiate between sterile inflammation and infection with S. aureus by imaging. Due to its physical properties, 18F is more favorable for PET/CT imaging. As peptide labeling with 18F is challenging, we here implemented the Al18F labeling approach. This study aims to develop an optimized, fully automated, GMP-compliant process for radiolabeling of NOTA-conjugated UBI(29–41) with Al18F for PET/CT imaging of infections.

Results

Optimized reaction conditions led to the establishment of a robust Al18Fcomplexation protocol, which was implemented on a SynChrom R&D module. The labeling reaction was carried out in an acidic medium (pH 4.0) at 105 °C for 15 min, followed by a two-step HPLC purification for 20 min. Optimization of reagent concentrations enabled an activity yield up to 10 ± 1 GBq, with a radiochemical yield of 24.2 ± 0.6% and an apparent molar activity of 45 ± 4 GBq/µmol at end of synthesis (EOS) (n = 3). The radiochemical purity was 96.6 ± 0.3% as determined by analytical HPLC, using UV absorption (220 nm). Quality control was successfully established using validated analytical procedures.

Conclusions

The developed GMP-compliant radiolabelling process yields reproducible results with sufficient activities for further translation and investigations of clinical PET/CT imaging using Al[18F]F-NOTA-UBI(29–41) in infectious diseases.