title: Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-alpha and interleukin-8.
abstract: This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-alpha (TNF-alpha) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus-or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 micrograms of the 99mTc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99mTc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99mTc-labeled polyclonal human immunoglobulin (IgG) and a 99mTc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99mTc-anti-TNF accumulated to a higher extent (p < 0.05) in S. aureus-infected thighs in mice until 4 h after the injection than 99mTc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p < 0.03) compared with 99mTc-IgG. In established S. aureus and K. pneumoniae infections, 99mTc-anti-IL-8 detected the infection more intensely than 99mTc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p < 0.05) with increased binding of the 99mTc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99mTc-labeled MAbs, directed against TNF-alpha and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99mTc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99mTc-labeled MAbs, information might be gained about the development of an infection.
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, University Hospital, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Welling
authors.forename: H I
authors.initials: HI
authors.lastname: Feitsma
authors.forename: W
authors.initials: W
authors.lastname: Calame
authors.forename: E K
authors.initials: EK
authors.lastname: Pauwels
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology*; D007553:Isotope Labeling; D007710:Klebsiella Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D007711:Klebsiella pneumoniae; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000382:microbiology; D011877:Radionuclide Imaging; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D013667:Technetium; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D013667:Technetium