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

Zhuo Zhang; Alvaro A. Ordonez; Hui Wang; Yong Li; Kayla R. Gogarty; Edward A. Weinstein; Fereidoon Daryaee; Jonathan Merino; Grace E. Yoon; Alvin S. Kalinda; Ronnie C. Mease; James N. Iuliano; Peter M. Smith-Jones; Sanjay K. Jain; Peter J. Tonge

doi:10.1021/acsinfecdis.8b00182

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

Zhuo Zhang, Alvaro A. Ordonez, Hui Wang, Yong Li, Kayla R. Gogarty, Edward A. Weinstein, Fereidoon Daryaee, Jonathan Merino, Grace E. Yoon, Alvin S. Kalinda, Ronnie C. Mease, James N. Iuliano, Peter M. Smith-Jones, Sanjay K. Jain, Peter J. Tonge

School of Medicine

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1635-1644
Number of pages	10
Journal	ACS Infectious Diseases
Volume	4
Issue number	11
DOIs	https://doi.org/10.1021/acsinfecdis.8b00182
State	Published - Nov 9 2018

Keywords

MRSA
PET
bacteria
folate
imaging
infection

ASJC Scopus subject areas

Infectious Diseases

Access to Document

10.1021/acsinfecdis.8b00182

Cite this

Zhang, Z., Ordonez, A. A., Wang, H., Li, Y., Gogarty, K. R., Weinstein, E. A., Daryaee, F., Merino, J., Yoon, G. E., Kalinda, A. S., Mease, R. C., Iuliano, J. N., Smith-Jones, P. M., Jain, S. K., & Tonge, P. J. (2018). Positron Emission Tomography Imaging with 2-[¹⁸F]F- p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response. ACS Infectious Diseases, 4(11), 1635-1644. https://doi.org/10.1021/acsinfecdis.8b00182

Zhang, Z, Ordonez, AA, Wang, H, Li, Y, Gogarty, KR, Weinstein, EA, Daryaee, F, Merino, J, Yoon, GE, Kalinda, AS, Mease, RC, Iuliano, JN, Smith-Jones, PM, Jain, SK & Tonge, PJ 2018, 'Positron Emission Tomography Imaging with 2-[¹⁸F]F- p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response', ACS Infectious Diseases, vol. 4, no. 11, pp. 1635-1644. https://doi.org/10.1021/acsinfecdis.8b00182

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abstract = "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.",

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