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MicroPET imaging of bacterial infection with nitroreductase-specific responsive 18F-labelled nitrogen mustard analogues

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Bacterial infection and antibiotic resistance are serious threats to human health. This study aimed to develop two novel radiotracers, 18F-NTRP and 18F-NCRP, that possess a specific nitroreductase (NTR) response to image deep-seated bacterial infections using positron emission tomography (PET). This method can distinguish infection from sterile inflammation.

Methods

18F-NTRP and 18F-NCRP were synthesized via a one-step method; all the steps usually involved in tracer radiosynthesis were successfully adapted in the All-In-One automated module. After the physiochemical properties of 18F-NTRP and 18F-NCRP were characterized, their specificity and selectivity for NTR were verified in E. coli and S. aureus. The ex vivo biodistribution of the tracers was evaluated in normal mice. MicroPET-CT imaging was performed in mouse models of bacterial infection and inflammation after the administration of 18F-NTRP or 18F-NCRP.

Results

Fully automated radiosynthesis of 18F-NTRP and 18F-NCRP was achieved within 90–110 min with overall decay-uncorrected, isolated radiochemical yields of 21.24 ± 4.25% and 11.3 ± 3.78%, respectively. The molar activities of 18F-NTRP and 18F-NCRP were 320 ± 40 GBq/μmol and 275 ± 33 GBq/µmol, respectively. In addition, 18F-NTRP and 18F-NCRP exhibited high selectivity and specificity for NTR response. PET-CT imaging in bacteria-infected mouse models with 18F-NTRP or 18F-NCRP showed significant radioactivity uptake in either E. coli– or S. aureus–infected muscles. The uptake for E. coli–infected muscles, 2.4 ± 0.2%ID/g with 18F-NTRP and 4.05 ± 0.49%ID/g with 18F-NCRP, was up to three times greater than that for uninfected control muscles. Furthermore, for both 18F-NTRP and 18F-NCRP, the uptake in bacterial infection was 2.6 times higher than that in sterile inflammation, allowing an effective distinction of infection from inflammation.

Conclusion

18F-NTRP and 18F-NCRP are worth further investigation to verify their potential clinical application for distinguishing bacterial infection from sterile inflammation via their specific NTR responsiveness.

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Funding

This study was supported by the National Natural Science Foundation of China (21976150), the Major Research Plan of the National Natural Science Foundation of China (91959122), and the Joint Fund of the National Natural Science Foundation of China and the China National Nuclear Corporation for Nuclear Technology Innovation (U1967222).

The experimental procedures, animal use, and care protocols were approved by the Institutional Animal Care and Use Committee of Xiamen University.

Author information

Author notes

  1. Lumei Huang and Jianyang Fang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, Fujian, China

    Lumei Huang, Jianyang Fang, Shouqiang Hong, Huanhuan Liu, Haotian Zhu, Lixia Feng, Rongqiang Zhuang, Xilin Zhao, Zhide Guo & Xianzhong Zhang

  2. Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, Fujian, China

    Lumei Huang, Jianyang Fang, Huanhuan Liu, Haotian Zhu, Lixia Feng, Rongqiang Zhuang, Zhide Guo & Xianzhong Zhang

  3. Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, 07103, USA

    Xilin Zhao

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  1. Lumei Huang
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Contributions

Conceptualization: Xianzhong Zhang, Lumei Huang, Jianyang Fang, Zhide Guo; methodology: Roangqiang Zhuang, Lumei Huang, Shouqiang Hong, and Xilin Zhao; formal analysis and investigation: Lumei Huang, Jianyang Fang, Huanhuan Liu, Haotian Zhu, Lixia Feng; writing (original draft preparation): Lumei Huang, Jianyang Fang; writing (review and editing): Xianzhong Zhang, Zhide Guo, Xilin Zhao; funding acquisition: Xianzhong Zhang, Zhide Guo; supervision: Xianzhong Zhang. All authors read and approved the final manuscript.

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Correspondence to Zhide Guo or Xianzhong Zhang.

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This article is part of the Topical Collection on Infection and inflammation

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Huang, L., Fang, J., Hong, S. et al. MicroPET imaging of bacterial infection with nitroreductase-specific responsive 18F-labelled nitrogen mustard analogues. Eur J Nucl Med Mol Imaging 49, 2645–2654 (2022). https://doi.org/10.1007/s00259-022-05710-2

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  • DOI: https://doi.org/10.1007/s00259-022-05710-2

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