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  • Title: Detection of thromboembolism with ⁹⁹mTc-labeled F(ab)₂ fragment of anti-glycoprotein IIIa chimeric monoclonal antibody in beagle canines.
    Author: Ji S, Fang W, Dong N, He Z, Ruan C.
    Journal: Thromb Res; 2012 Nov; 130(5):703-8. PubMed ID: 22967949.
    Abstract:
    INTRODUCTION: 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. MATERIALS AND 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.
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