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Purpose

Bacterial infection and antibiotic-resistant are still serious threats to human health. Here, we aim to develop two novel radiotracers 18 F-NTRP and 18 F-NCRP with specific nitroreductase (NTR) responsive to image the deep-seated bacterial infection with PET for differentiating infection from sterile inflammation.

Methods

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

Results

Fully automated radiosynthesis of 18 F-NTRP and 18 F-NCRP were achieved within 90-110 min with overall decay-uncorrected isolated radiochemical yields of 21.24±4.25% and 11.3±3.78% respectively. Molar activities of 18 F-NTRP and 18 F-NCRP were 320±40 GBq/µmol and 275±33 GBq/µmol respectively. In addition, 18 F-NTRP and 18 F-NCRP exhibited good selectivity and specificity to NTR response. PET-CT imaging in bacterial infected mice models with 18 F-NTRP and 18 F-NCRP showed significant radioactivity uptakes in both E. coli and S. aureus infected muscles. Especially, the E. coli infected muscle uptakes were up to 2.4±0.2% ID/g (18 F-NTRP) and 4.05±0.49% ID/g (18 F-NCRP), 3-fold to control uptake. Furthermore, both 18 F-NTRP and 18 F …