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11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans
Alvaro A. Ordonez, … , David M. Wilson, Sanjay K. Jain
Alvaro A. Ordonez, … , David M. Wilson, Sanjay K. Jain
Published January 11, 2022
Citation Information: JCI Insight. 2022;7(1):e154117. https://doi.org/10.1172/jci.insight.154117.
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Resource and Technical Advance Infectious disease

11C-Para-aminobenzoic acid PET imaging of S. aureus and MRSA infection in preclinical models and humans

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Abstract

Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus–infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

Authors

Alvaro A. Ordonez, Matthew F.L. Parker, Robert J. Miller, Donika Plyku, Camilo A. Ruiz-Bedoya, Elizabeth W. Tucker, Justin M. Luu, Dustin A. Dikeman, Wojciech G. Lesniak, Daniel P. Holt, Robert F. Dannals, Lloyd S. Miller, Steven P. Rowe, David M. Wilson, Sanjay K. Jain

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Figure 1

11C-PABA PET/CT imaging in a rabbit myositis model.

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11C-PABA PET/CT imaging in a rabbit myositis model.
(A) New Zealand whi...
(A) New Zealand white rabbits were infected with live bacteria (E. coli or S. aureus) in the right triceps and injected with heat-killed bacteria at 10 times the level of live bacteria in the contralateral triceps (left). Coronal and traverse 11C-PABA PET/CT imaging of a representative E. coli–infected rabbit (right). The 11C-PABA PET signal was observed at the site of infection (live bacteria) with minimum signal associated with the site of sterile inflammation (heat-killed bacteria). (B) The 11C-PABA PET signal in rabbits infected with E. coli (n = 3) and S. aureus (n = 4), quantified as ratio to blood. (C) Comparison of the volume of interest (VOI) quantification of 11C-PABA PET, determined as the infection vs. inflammation target-to-nontarget (TNT) ratio of E. coli and S. aureus–infected animals (left). Comparison of the 11C-PABA PET infection vs. unaffected muscle TNT ratio of E. coli and S. aureus–infected animals (right). (D) TNT ratio of S. aureus–infected animals imaged with 18F-FDG PET (n = 3). All Data are represented as the median ± IQR. Statistical comparisons were performed using a 1-way ANOVA with Tukey’s multiple-comparisons test.

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