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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 3

Imaging a vertebral discitis-osteomyelitis rat model using 11C-PABA.

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Imaging a vertebral discitis-osteomyelitis rat model using 11C-PABA.
(A)...
(A) In rats, the third intervertebral segments distal to the coat/tail transition were inoculated with live S. aureus. Heat-killed bacteria were injected into the fifth intervertebral space to induce sterile inflammation. (B) Optical imaging on day 3 after inoculation. Site of injection of bioluminescent S. aureus is visible and localized. (C) Coronal, transverse, and sagittal PET/CT images of 11C-PABA on day 4 after inoculation with bioluminescent S. aureus. Uptake of 11C-PABA is visible and localized at the site of live infection (third intervertebral space). The sagittal PET/CT image shows absent signal at site of sterile inflammation (fifth intervertebral space) or unaffected intervertebral disc space (seventh intervertebral space). (D) VOI analysis of 11C-PABA PET on day 4 after inoculation with bioluminescent S. aureus (n = 5). Data are represented as the median ± IQR of the infection vs. inflammation and infection vs. unaffected target-to-nontarget ratio.

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