title: 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.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany.|Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Rostock, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Warnke
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Rolle
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schütz
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Oberhettinger
authors.affiliation: Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.affiliation: Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maurer
authors.affiliation: Biosciences and ISCA Diagnostics Ltd., University of Exeter, Exeter, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Thornton
authors.affiliation: CheMatech, Faculté des Sciences Mirande, Dijon, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Boschetti
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Autenrieth
mesh_terms: D000085:Acetates / Q000494:pharmacology; D018829:Adhesins, Bacterial / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D003301:Copper Radioisotopes; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D015009:Yersinia Infections / Q000000981:diagnostic imaging*; D015008:Yersinia enterocolitica
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C064832:YadA protein, Yersinia
keywords: 64Cu; Immune response; Immunity; Immunology and Microbiology Section; PET/MR; antibody; bacteria; in vivo imaging