Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis

Author:

Parker Matthew F L12,López-Álvarez Marina1,Alanizi Aryn A1,Luu Justin M1,Polvoy Ilona1,Sorlin Alexandre M1,Qin Hecong1,Lee Sanghee1,Rabbitt Sarah J1,Pichardo-González Priamo A1,Ordonez Alvaro A3,Blecha Joseph1,Rosenberg Oren S4,Flavell Robert R1,Engel Joanne45,Jain Sanjay K3,Ohliger Michael A16,Wilson David M1

Affiliation:

1. Department of Radiology and Biomedical Imaging, University of California , San Francisco

2. Department of Psychiatry, Renaissance School of Medicine at Stony Brook University , New York

3. Center for Infection and Inflammation Imaging Research, Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland

4. Department of Medicine, University of California, San Francisco

5. UCSF Department of Microbiology and Immunology, San Francisco, California

6. Department of Radiology, Zuckerberg San Francisco General Hospital , San Francisco, California

Abstract

Abstract Background Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported. Methods We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli. Results In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS. Conclusions Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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