Detection of Thromboembolism with 99mTc-labeled F(ab)2 Fragment of Anti-glycoprotein IIIa Chimeric Monoclonal Antibody in Beagle Canines

IntroductionRapid 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 99mTc-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 MethodsFlow 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 99mTc-chSZ21-F(ab)2 injection,animals were imaged for up to 3 hours then heparinized and sacrificed.ResultsSpecific 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% (IC50) 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.ConclusionsThese results suggested that 99mTc-chSZ21-F(ab)2 with high DVT and PE uptake is a promising agent for imaging vascular thrombosis.