title: The Positron Emission Tomography Tracer 3'-Deoxy-3'-[18F]Fluorothymidine ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic Yersinia enterocolitica Infection in Mice.
abstract: Most frequently, gram-negative bacterial infections in humans are caused by Enterobacteriaceae and remain a major challenge in medical diagnostics. We non-invasively imaged moderate and severe systemic Yersinia enterocolitica infections in mice using the positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which is a marker of proliferation, and compared the in vivo results to the ex vivo biodistributions, bacterial loads, and histologies of the corresponding organs. Y. enterocolitica infection is detectable with histology using H&E staining and immunohistochemistry for Ki 67. [18F]FLT revealed only background uptake in the spleen, which is the main manifestation site of systemic Y. enterocolitica-infected mice. The uptake was independent of the infection dose. Antibody-based thymidine kinase 1 (Tk-1) staining confirmed the negative [18F]FLT-PET data. Histological alterations of spleen tissue, observed via Ki 67-antibody-based staining, can not be detected by [18F]FLT-PET in this model. Thus, the proliferation marker [18F]FLT is not a suitable tracer for the diagnosis of systemic Y. enterocolitica infection in the C57BL/6 animal model of yersiniosis.
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0003-1923-765X
authors.initials: S
authors.lastname: Wiehr
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, Tübingen, Germany.|Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Warnke
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: Gerald
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Institute of Medical Microbiology and Hygiene, Eberhard Karls University Tübingen, 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: D000818:Animals; D058491:Bacterial Load; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D015009:Yersinia Infections / Q000000981:diagnostic imaging*; D015008:Yersinia enterocolitica / Q000502:physiology*
chemical_list: D011849:Radioactive Tracers; D019275:Radiopharmaceuticals