title: Detection of thromboembolism with ⁹⁹mTc-labeled F(ab)₂ fragment of anti-glycoprotein IIIa chimeric monoclonal antibody in beagle canines.
abstract: BACKGROUND
  Rapid and timely diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) is important to improve patient outcome. The goal of this study was using (99m)Tc-chSZ21-F(ab)(2), F(ab)(2) fragment of anti-glycoprotein IIIa chimeric monoclonal antibody, to image experimental thromboembolism (DVT and PE) in dogs.
  
  
  METHODS
  Flow cytometry assay and adenosine diphosphate (ADP) stimulated platelet aggregation was performed to determine the specificity and affinity of chSZ21-F(ab)(2) to the GPIIb/IIIa receptor on human or canine platelets. Both PE and DVT were induced in 12 beagle canines by catheter under X-ray direction. After (99m)Tc-chSZ21-F(ab)(2) injection,animals were imaged for up to 3 hours then heparinized and sacrificed.
  
  
  RESULTS
  Specific binding of chSZ21-F (ab)(2) to GPIIb/IIIa on human or canine platelets was verified by flow cytometry assay. chSZ21-F (ab)(2) inhibited ADP induced platelet aggregation with a dose-dependent manner, the concentration required to inhibit 50% (IC(50)) of platelet aggregation was 11.6 ± 7.9 nM and 24.9 ± 18.8 nM for human and canine, respectively. In vivo, focal uptake was observed in planar images as early as 30 min (DVT) and 60 min (PE), and became clearer within 3 hours after injection. Lesion-to-background ratio averaged 12.8 (PE-to-lung), 7.2 (DVT-to-blood), and 117.0(DVT-to-muscle), respectively.
  
  
  CONCLUSIONS
  These results suggested that (99m)Tc-chSZ21-F(ab)(2) with high DVT and PE uptake is a promising agent for imaging vascular thrombosis.
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, China 188 Shizi Street, Suzhou, Jiangsu, China, 215006.
authors.forename: Shundong
authors.initials: S
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.forename: Ningzheng
authors.initials: N
authors.lastname: Dong
authors.forename: Zuoxiang
authors.initials: Z
authors.lastname: He
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004285:Dogs; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000276:immunology; D008297:Male; D051379:Mice; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging* / Q000276:immunology*; D019275:Radiopharmaceuticals / Q000276:immunology; D011993:Recombinant Fusion Proteins; D017556:Technetium Compounds / Q000276:immunology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D017556:Technetium Compounds