We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
MicroPET imaging of bacterial infection with nitroreductase-specific responsive <sup>18</sup>F-labelled nitrogen mustard analogues.
- Authors
Huang, Lumei; Fang, Jianyang; Hong, Shouqiang; Liu, Huanhuan; Zhu, Haotian; Feng, Lixia; Zhuang, Rongqiang; Zhao, Xilin; Guo, Zhide; Zhang, Xianzhong
- 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.
- Subjects
POSITRON emission tomography; BACTERIAL diseases; NITROREDUCTASES; INFLAMMATION; RADIOACTIVITY
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2022, Vol 49, Issue 8, p2645
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-022-05710-2