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

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalACS Infectious Diseases
DOIs
StateAccepted/In press - Jan 1 2018

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Keywords

  • Bacteria
  • folate
  • imaging
  • infection
  • MRSA
  • PET

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

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