Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

Christopher A. Mutch, Alvaro A. Ordonez, Hecong Qin, Matthew Parker, Lauren E. Bambarger, Javier E. Villanueva-Meyer, Joseph Blecha, Valerie Carroll, Celine Taglang, Robert Flavell, Renuka Sriram, Henry Vanbrocklin, Oren Rosenberg, Michael A. Ohliger, Sanjay K. Jain, Kiel D. Neumann, David M. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Imaging studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently, there is significant overlap in the imaging appearance of infectious and noninfectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabeled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study, we developed an efficient radiosynthesis for [11C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.

Original languageEnglish (US)
Pages (from-to)1067-1072
Number of pages6
JournalACS Infectious Diseases
Volume4
Issue number7
DOIs
StatePublished - Jul 13 2018

Keywords

  • bacteria
  • folate
  • infection
  • metabolism
  • positron emission tomography

ASJC Scopus subject areas

  • Infectious Diseases

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