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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 4

Biodistribution of 11C-PABA in healthy humans.

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Biodistribution of 11C-PABA in healthy humans.
(A) Sequential 11C-PABA P...
(A) Sequential 11C-PABA PET maximum intensity projection of a representative healthy human participant. For this participant, 11C-PABA was injected into the median cubital vein of the left arm. All images were adjusted to the same mean SUV. (B) Coronal and transverse 11C-PABA PET/CT sections of participant no. 1 at 30 minutes after injection. (C) Tissue biodistribution of 11C-PABA 30 minutes after injection. Data are represented as the median percentage injected dose per cc (%ID/cc), IQR (boxes), and range (whiskers show minimum and maximum values) (n = 5 participants). (D) Time-activity curves of 11C-PABA in the brain, lungs, liver, and muscle of healthy humans. Data are represented as the median ± IQR (n = 5 participants).

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