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

被引：64

作者：

Zhang, Zhuo ^{[1
]}

Ordonez, Alvaro A. ^{[2
,3
]}

Wang, Hui ^{[1
]}

Li, Yong ^{[1
]}

Gogarty, Kayla R. ^{[1
]}

Weinstein, Edward A. ^{[2
]}

Daryaee, Fereidoon ^{[1
]}

Merino, Jonathan ^{[1
]}

Yoon, Grace E. ^{[1
,5
]}

Kalinda, Alvin S. ^{[2
,3
]}

Mease, Ronnie C. ^{[4
]}

Iuliano, James N. ^{[1
]}

Smith-Jones, Peter M. ^{[5
]}

Jain, Sanjay K. ^{[2
,3
,4
]}

Tonge, Peter J. ^{[1
]}

机构：

[1] SUNY Stony Brook, Dept Chem & Radiol, Inst Chem Biol & Drug Discovery, 100 Nicolls Rd,633 Chem, Stony Brook, NY 11794 USA

[2] Johns Hopkins Univ, Ctr Infect & Inflammat Imaging Res, Sch Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA

[5] SUNY Stony Brook, Dept Psychiat, Facil Expt Radiopharmaceut Mfg, Stony Brook, NY 11794 USA

来源：

ACS INFECTIOUS DISEASES | 2018年 / 4卷 / 11期

关键词：

bacteria; PET; imaging; infection; folate; MRSA; PARA-AMINOBENZOIC ACID; BACTERIAL-INFECTIONS; PET; TRACER; FDG;

D O I：

10.1021/acsinfecdis.8b00182

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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-[F-18]F-PABA) and demonstrate that it is an efficient alternative substrate for the S. aureus dihydropteroate synthase (DHPS). 2-[F-18]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-[F-18]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-[F-18]F-PABA has the potential for translation to humans as a rapid, noninvasive diagnostic tool to identify, localize, and monitor S. aureus infections.

引用

页码：1635 / 1644

页数：10

共 42 条

[1] Kinetic modeling of [18F]FDG in skeletal muscle by PET:: a four-compartment five-rate-constant model [J].