MicroPET imaging of bacterial infection with nitroreductase-specific responsive 18F-labelled nitrogen mustard analogues.
Eur J Nucl Med Mol Imaging
; 49(8): 2645-2654, 2022 07.
Article
en En
| MEDLINE
| ID: mdl-35122512
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones Bacterianas
/
Mecloretamina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
China