title: Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.
abstract: We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin.
  
  
  METHODS
  Rats received an intravenous injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed. After death, tissue was removed and activity was measured, lungs were cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-1alpha was examined on blood polymorphonuclear leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis.
  
  
  RESULTS
  In rats injected with (111)In*aICAM-1, the percent injected dose/organ in lungs both at 4 and 24 hr postbleomycin increased significantly compared to the values in either uninjured rats or rats that received (111)In*nmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For (111)In*nmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In (111)In*aICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood-pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs. Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values.
  
  
  CONCLUSIONS
  Biodistribution and imaging data demonstrate that (111)In*aICAM-1 can detect early acute bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that (111)In*ICAM-1 uptake is a specific process. This antibody has potential as an early radionuclide detector of acute inflammations.
authors.affiliation: Department of Diagnostic Imaging, University of Connecticut Health Center, Farmington 06030, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Weiner
authors.forename: D E
authors.initials: DE
authors.lastname: Sasso
authors.forename: M A
authors.initials: MA
authors.lastname: Gionfriddo
authors.forename: S I
authors.initials: SI
authors.lastname: Syrbu
authors.forename: H M
authors.initials: HM
authors.lastname: Smilowitz
authors.forename: J
authors.initials: J
authors.lastname: Vento
authors.forename: R S
authors.initials: RS
authors.lastname: Thrall
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001761:Bleomycin; D002951:Citrates; D005455:Fluorescent Antibody Technique; D005708:Gallium; D007074:Immunoglobulin G / Q000276:immunology; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology*; D008168:Lung / Q000737:chemistry / Q000000981:diagnostic imaging; D008171:Lung Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D016719:Radioimmunodetection; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D002951:Citrates; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D016169:Lymphocyte Function-Associated Antigen-1; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1; D005708:Gallium; C103850:gallium citrate