Oncotarget

Research Papers: Immunology:

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

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 _

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Oncotarget. 2016; 7:10990-11001. https://doi.org/10.18632/oncotarget.7770

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Abstract

Stefan Wiehr1, Philipp Warnke2,7, Anna-Maria Rolle1, Monika Schütz2, Philipp Oberhettinger2, Ursula Kohlhofer3, Leticia Quintanilla-Martinez3, Andreas Maurer1, Christopher Thornton4, Frederic Boschetti5, Gerald Reischl1, Ingo B. Autenrieth2, Bernd J. Pichler1 and Stella E. Autenrieth6

1 Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany

2 Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany

3 Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany

4 Biosciences and ISCA Diagnostics Ltd., University of Exeter, Exeter, United Kingdom

5 CheMatech, Faculté des Sciences Mirande, Dijon, France

6 Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany

7 Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Rostock, Germany

Correspondence to:

Stella E. Autenrieth, email:

Keywords: bacteria, PET/MR, in vivo imaging, 64Cu, antibody, Immunology and Microbiology Section, Immune response, Immunity

Received: October 01, 2015 Accepted: February 20, 2016 Published: February 26, 2016

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.


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