New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection.

Abstract

The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [64Cu]NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [18F]FDG, [64Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [64Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions.

• Authors: Stefan Wiehr, Philipp Warnke, Anna-Maria Rolle, Monika Schütz, Philipp Oberhettinger, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Andreas Maurer, Christopher Thornton, Frederic Boschetti, Gerald Reischl, Ingo B Autenrieth, Bernd J Pichler, Stella E Autenrieth
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 10 Pg. 10990-1001 (Mar 08 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26934329 (Publication Type: Journal Article)

Chemical References

• 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
• Acetates
• Adhesins, Bacterial
• Antibodies, Bacterial
• Copper Radioisotopes
• Heterocyclic Compounds, 1-Ring
• Radiopharmaceuticals
• YadA protein, Yersinia

Topics

• Acetates (pharmacology)
• Adhesins, Bacterial (immunology)
• Animals
• Antibodies, Bacterial (immunology)
• Copper Radioisotopes
• Female
• Heterocyclic Compounds, 1-Ring (pharmacology)
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred C57BL
• Molecular Imaging (methods)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (pharmacology)
• Yersinia Infections (diagnostic imaging)
• Yersinia enterocolitica