Differentiation Between Responders and Non-Responders to Antibiotic Treatment in Mice Using 18F-Fluorodeoxysorbitol/PET.

IF 3 4区 医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Junling Li, Huaiyu Zheng, Jenna Olson, Jonathan M Warawa, Chin K Ng
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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 18F-Fluorodeoxysorbitol (18F-FDS) or 18F-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. 18F-FDS or 8F-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. 18F-FDG was used to compare with 18F-FDS, but all mice showed increased lung uptake of 18F-FDG during 3-day treatments.

Conclusions: 18F-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 18F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.

利用 18F-Fluorodeoxysorbitol/PET 对抗生素治疗小鼠的应答者和非应答者进行区分。
目的:尽管有抗生素可用,细菌感染仍会在全球范围内导致大量死亡和发病。在抗生素治疗的早期阶段区分应答者和非应答者将为患者和医疗服务提供者提供信息。我们的目的是研究 18F-FDS 或 18F-FDG PET 成像是否可用于区分抗生素治疗的应答者和非应答者:用NTUH-K2044感染白化C57雌性小鼠。每只小鼠气管内接种 NTUH-K2044 以诱导肺部感染(n = 8)。在治疗研究中,比较了动物接种的两种细菌剂量和两种治疗开始时间,以优化治疗方案。18F-FDS或8F-FDG /PET成像用于监测治疗进展:结果:我们的研究结果表明,小鼠感染 25 CFU hvKp 并在 24 p.i. 开始抗生素治疗的治疗方案并不理想,因为没有肺部感染的证据,而且缺乏疗效。最佳方案是使用 250 CUF 进行感染,并在 24 小时后开始抗生素治疗,以监测抗菌效果。75%的小鼠对抗生素治疗有反应。25%的小鼠被归类为无应答者。18F-FDG被用来与18F-FDS进行比较,但在3天的治疗过程中,所有小鼠的肺部摄取18F-FDG都有所增加:结论:18F-FDS 是一种很有前景的用于细菌感染成像的 PET 示踪剂。结论:18F-FDS 是一种很有前途的正电子发射计算机示踪剂,可用于监测对治疗的反应,并区分对抗生素治疗有反应者和无反应者,但 18F-FDG 却不能,这可能是由于治疗前后存在高度炎症。
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来源期刊
CiteScore
6.90
自引率
3.20%
发文量
95
审稿时长
3 months
期刊介绍: Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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