Background To the present day infective endocarditis (IE) represents a life-threatening disease with high mortality rate especially when caused by Staphylococcus aureus (S. aureus), the most common causative pathogen in this disease. Diagnosis of IE is based on clinical manifestations, pathogen detection by blood cultures and echocardiographic or other imaging findings. However, none of the methods used is capable of detecting the causative bacterial cells on the endothelium directly. Modern molecular imaging such as positron emission tomography/computed tomography (PET/CT) is playing an increasingly important role in unclear IE cases. This study focused on 2-[18F]F-p-aminobenzoic acid (2-[18F]F-PABA), a bacteria specific tracer for the diagnosis of IE using PET imaging for direct pathogen detection. Methods In vitro assays were performed to analyze 2-[18F]F-PABA uptake by S. aureus. For proof-of-concept in vivo trials an endocarditis mouse model was used to diagnose IE by PET/Magnetic resonance (MR) imaging. A subcutaneous abscess mouse model was supplemented to create larger bacterial vegetations for PET imaging. Results 2-[18F]F-PABA in vitro uptake by S. aureus was confirmed. Only living bacteria were able to accumulate the tracer while the extent of uptake varied between different S. aureus strains. In the in vivo proof-of-concept, IE was visualized in mice using 2-[18F]F-PABA-PET/MR imaging. Subsequently, 2-[18F]F-PABA specifically located S. aureus vegetations in the subcutaneous abscess model. Conclusions This study highlights the great potential of 2-[18F]F-PABA imaging for the direct detection of IE. Future studies might further investigate the clinical potential of this molecular imaging approach, finally aiming at a clinical implementation.

中文翻译：

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2-[18F]F-对氨基苯甲酸在正电子发射断层扫描中特异性检测感染性心内膜炎


背景 迄今为止，感染性心内膜炎 （IE） 是一种危及生命且死亡率高的疾病，尤其是由金黄色葡萄球菌 （S. aureus） 引起时，金黄色葡萄球菌是该疾病中最常见的致病病原体。IE 的诊断基于临床表现、血培养和超声心动图或其他影像学检查结果的病原体检测。然而，所使用的方法都不能直接检测内皮上的致病细菌细胞。现代分子成像，如正电子发射断层扫描/计算机断层扫描 （PET/CT），在不明确的 IE 病例中发挥着越来越重要的作用。本研究的重点是 2-[18F]F-对氨基苯甲酸 （2-[18F]F-PABA），这是一种使用 PET 成像直接检测病原体诊断 IE 的细菌特异性示踪剂。方法 进行体外测定分析金黄色葡萄球菌对 2-[18F]F-PABA 的摄取。对于概念验证体内试验，使用心内膜炎小鼠模型通过 PET/磁共振 （MR） 成像诊断 IE。补充皮下脓肿小鼠模型以创建更大的细菌赘生物用于 PET 成像。结果 2-[18F]F-PABA 在金黄色葡萄球菌体外摄取得到证实。只有活细菌能够积累示踪剂，而不同金黄色葡萄球菌菌株的摄取程度不同。在体内概念验证中，使用 2-[18F]F-PABA-PET/MR 成像在小鼠中可视化 IE。随后，2-[18F]F-PABA 在皮下脓肿模型中特异性定位了金黄色葡萄球菌赘生物。结论 本研究强调了 2-[18F]F-PABA 成像直接检测 IE 的巨大潜力。未来的研究可能会进一步调查这种分子成像方法的临床潜力，最终以临床实施为目标。