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