Positron Emission Tomography Imaging with 2-[18F]F- p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response.,ACS Infectious Diseases

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Positron Emission Tomography Imaging with 2-[18F]F- p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-08-17 , DOI: 10.1021/acsinfecdis.8b00182
Zhuo Zhang ₁ , Alvaro A Ordonez _{2,

3} , Hui Wang ₁ , Yong Li ₁ , Kayla R Gogarty ₁ , Edward A Weinstein ₂ , Fereidoon Daryaee ₁ , Jonathan Merino ₁ , Grace E Yoon _{1,

4} , Alvin S Kalinda _{2,

3} , Ronnie C Mease ₅ , James N Iuliano ₁ , Peter M Smith-Jones ₄ , Sanjay K Jain _{2,

3,

5} , Peter J Tonge ₁

Affiliation

Staphylococcus aureus is the leading cause of life-threatening infections, frequently originating from unknown or deep-seated foci. Source control and institution of appropriate antibiotics remain challenges, especially with infections due to methicillin-resistant S. aureus (MRSA). In this study, we developed a radiofluorinated analog of para-aminobenzoic acid (2-[18F]F-PABA) and demonstrate that it is an efficient alternative substrate for the S. aureus dihydropteroate synthase (DHPS). 2-[18F]F-PABA rapidly accumulated in vitro within laboratory and clinical (including MRSA) strains of S. aureus but not in mammalian cells. Biodistribution in murine and rat models demonstrated localization at infection sites and rapid renal elimination. In a rat model, 2-[18F]F-PABA positron emission tomography (PET) rapidly differentiated S. aureus infection from sterile inflammation and could also detect therapeutic failures associated with MRSA. These data suggest that 2-[18F]F-PABA has the potential for translation to humans as a rapid, noninvasive diagnostic tool to identify, localize, and monitor S. aureus infections.

中文翻译：

用2- [18F] F-对氨基苯甲酸进行正电子发射断层显像，可检测金黄色葡萄球菌感染并监测药物反应。

金黄色葡萄球菌是威胁生命的感染的主要原因，通常源于未知或深部病灶。来源控制和适当抗生素的使用仍然是挑战，尤其是对耐甲氧西林的金黄色葡萄球菌（MRSA）造成的感染。在这项研究中，我们开发了对氨基苯甲酸（2- [18F] F-PABA）的放射性氟化类似物，并证明它是金黄色葡萄球菌二氢蝶呤合酶（DHPS）的有效替代底物。2- [18F] F-PABA在金黄色葡萄球菌的实验室和临床菌株（包括MRSA）中在体外迅速积累，但在哺乳动物细胞中却没有迅速积累。在鼠类和大鼠模型中的生物分布证明其位于感染部位并迅速消除肾脏。在大鼠模型中，2- [18F] F-PABA正电子发射断层扫描（PET）快速区分S。金黄色葡萄球菌感染是由无菌炎症引起的，也可能检测出与MRSA相关的治疗失败。这些数据表明2- [18F] F-PABA具有作为识别，定位和监测金黄色葡萄球菌感染的快速，非侵入性诊断工具而向人类翻译的潜力。

更新日期：2018-08-01

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