Introduction

Bacterial infections pose major challenges in medicine. To guide effective infection treatment, faster and more accurate diagnostic modalities are needed. Bacteria-targeted molecular imaging can meet these needs. The present study was aimed at the in vivo evaluation of two ¹⁸F-vancomycin-based PET tracers, for detection of deep-seated Gram-positive bacterial infections. These tracers were bench-marked against the current standard of care, [¹⁸F]FDG.

Methods

The potential of [¹⁸F]BODIPY-FL-vancomycin and [¹⁸F]PQ-VE1-vancomycin ([4+2]photocycloadduct of 9,10-phenanthrenequinone-vancomycin and [¹⁸F]fluorinated vinyl ether) to distinguish bacterial infections from sterile inflammation was evaluated in a murine myositis model. Tracer specificity was assessed by infecting mice either with the Gram-positive bacterium Staphylococcus aureus (n = 12) or the Gram-negative bacterium Escherichia coli (n = 12). The contralateral leg was injected with Cytodex beads to induce sterile inflammation, or with phosphate-buffered saline for control. In parallel, mice were imaged with [¹⁸F]FDG (n = 12). Dynamic positron emission tomography (PET) measurements, biodistribution analyses, and immunohistopathology were performed to determine tracer distribution and bacterial burden.

Results

Both ¹⁸F-vancomycin-PET tracers accumulated at sites of infection, but not at sites of sterile inflammation, in contrast to [¹⁸F]FDG. The tracers exhibited distinct biodistribution profiles, with [¹⁸F]BODIPY-FL-vancomycin being cleared more rapidly. Both ¹⁸F-vancomycin-PET tracers displayed significant target to non-target ratios of 2.95 for [¹⁸F]BODIPY-FL-vancomycin and 1.48 for [¹⁸F]PQ-VE1-vancomycin.

Conclusion

Vancomycin-based PET is a potentially attractive approach to distinguish Gram-positive bacterial infections from sterile inflammation.

中文翻译：

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使用基于万古霉素的正电子发射计算机断层显像示踪剂进行细菌靶向成像可以区分感染和无菌性炎症

 介绍

细菌感染在医学上构成了重大挑战。为了指导有效的感染治疗，需要更快、更准确的诊断方式。细菌靶向分子成像可以满足这些需求。本研究旨在对两种基于 ¹⁸种 F-万古霉素的 PET 示踪剂进行体内评估，以检测根深蒂固的革兰氏阳性菌感染。这些示踪剂根据当前的护理标准 [¹⁸F]FDG 进行了基准标记。

 方法

在小鼠肌炎模型中评估了 [¹⁸F]BODIPY-FL-万古霉素和 [¹⁸F]PQ-VE1-万古霉素（9,10-菲醌-万古霉素和 [¹⁸F] 氟化乙烯基醚的 [4+2] 光环加合物）区分细菌感染和无菌性炎症的潜力。通过用革兰氏阳性菌金黄色葡萄球菌 （n = 12） 或革兰氏阴性菌大肠杆菌 （n = 12） 感染小鼠来评估示踪剂特异性。注射对侧腿 Cytodex 珠子以诱导无菌炎症，或注射磷酸盐缓冲盐水以控制。同时，用 [¹⁸F]FDG （n = 12） 对小鼠进行成像。进行动态正电子发射断层扫描 （PET） 测量、生物分布分析和免疫组织病理学以确定示踪剂分布和细菌负荷。

 结果

与 [¹⁸F]FDG 相比，¹⁸个 F-万古霉素-PET 示踪剂都在感染部位积累，但在无菌性炎症部位没有积累。示踪剂表现出不同的生物分布特征，[¹⁸F]BODIPY-FL-万古霉素被更快地清除。两种 ¹⁸个 F-万古霉素-PET 示踪剂的靶标与非靶标比均显示 [¹⁸F]BODIPY-FL-万古霉素为 2.95，[¹⁸F]PQ-VE1-万古霉素为 1.48。

 结论

基于万古霉素的 PET 是区分革兰氏阳性菌感染和无菌性炎症的一种潜在有吸引力的方法。