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使用F-氟代脱氧山梨醇/PET区分小鼠抗生素治疗的应答者与无应答者。

Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using F-Fluorodeoxysorbitol/PET.

作者信息

Li Junling, Zheng Huaiyu, Olson Jenna, Warawa Jonathan M, Ng Chin K

机构信息

Department of Radiology, University of Louisville, 530 S Jackson Street, CCB-C07, Louisville, KY, 40202, USA.

Department of Radiology, University of Louisville, Louisville, KY, 40202, USA.

出版信息

Mol Imaging Biol. 2024 Dec;26(6):934-942. doi: 10.1007/s11307-024-01957-3. Epub 2024 Oct 15.

Abstract

PURPOSE

Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with F-Fluorodeoxysorbitol (F-FDS) or F-FDG can be used to differentiate responders from non-responders to antibiotic treatment.

PROCEDURES

NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratracheally with NTUH-K2044 to induce lung infection (n = 8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. F-FDS or F-FDG /PET imaging was performed to monitor treatment progression.

RESULTS

Our results demonstrated that the treatment profiles for mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. F-FDG was used to compare with F-FDS, but all mice showed increased lung uptake of F-FDG during 3-day treatments.

CONCLUSIONS

F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.

摘要

目的

尽管有抗生素可用,但细菌感染在全球范围内仍导致大量死亡和发病。在抗生素治疗早期区分反应者和无反应者,对患者和医疗服务提供者都具有指导意义。我们的目的是研究使用F-氟脱氧山梨醇(F-FDS)或F-FDG进行正电子发射断层扫描(PET)成像是否可用于区分抗生素治疗的反应者和无反应者。

程序

使用NTUH-K2044感染白化病C57雌性小鼠。每只小鼠经气管内接种NTUH-K2044以诱导肺部感染(n = 8)。在治疗研究中,比较了两种动物接种细菌剂量和两个治疗开始时间,以优化治疗方案。进行F-FDS或F-FDG/PET成像以监测治疗进展。

结果

我们的结果表明,感染25 CFU高毒力肺炎克雷伯菌且在感染后24小时开始抗生素治疗的小鼠的治疗方案不理想,因为没有肺部感染的证据且缺乏治疗效果。最佳方案是使用250 CUF进行感染,并在感染后24小时开始抗生素治疗以监测抗菌效果。75%的小鼠被归类为抗生素治疗的反应者。25%的小鼠被归类为无反应者。使用F-FDG与F-FDS进行比较,但在为期3天的治疗期间,所有小鼠的肺部F-FDG摄取均增加。

结论

F-FDS是一种有前景的用于细菌感染成像的PET示踪剂。它可用于监测治疗反应,并区分抗生素治疗的反应者和无反应者,但F-FDG不能,可能是由于治疗前后存在高度炎症。

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