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Detection of Thromboembolism with (99m)Tc-labeled F(ab)(2) Fragment of Anti-glycoprotein IIIa Chimeric Monoclonal Antibody in Beagle Canines.
Thromb Res. 2012 Sep 8;
Authors: Ji S, Fang W, Dong N, He Z, Ruan C
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 3hours 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±7.9nM and 24.9±18.8nM for human and canine, respectively. In vivo, focal uptake was observed in planar images as early as 30min (DVT) and 60min (PE), and became clearer within 3hours 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.
PMID: 22967949 [PubMed - as supplied by publisher]