Imaging Thromboembolism with ^99mtc Labelled Chimeric Monoclonal Anti-Platelet Glycoprotein Iiia Antibody Fragment chSZ21F(ab)₂: Evaluation In Beagle Canines

A mouse/human chimeric monoclonal antibody F(ab)₂ fragment, with high affinity for platelet glycoprotein IIIa was labelled with^99mTc (^99mTc-chSZ21F(ab)₂), and evaluated in canine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE).

ADP-stimulated platelet aggregation was performed to determine the affinity and specificity of chSZ21F(ab)₂ to the GPIIb/IIIa receptor on plates of human or canine. ChSZ21F(ab)₂ was modified with 2-iminotholane and incubated with ^99mTc-glucoheptonate for imaging of 24-h-old DVT and PE in a canine model. Animals were imaged for up to 3 h after injection, heparinized, and sacrificed. Lungs and other tissues, including blood and normal lungs, were harvested and, concurrently, ^99mTc was counted for determination of target to tissue ratios and the percentage of injected dose per gram of tissue.

The concentration of chSZ21F(ab)₂ required to inhibit 50% of platelet aggregation (IC₅₀) in platelet-rich plasma was 11.6±7.9 nM for human and 24.9±18.8 nM for canine. In vivo, focal uptake was observed in planar images as early as 30 min (DVT), and 60 min (PE) after injection. Lesion uptake of ^99mTc-chSZ21F(ab)₂ at 3 h after injection was calculated in terms of percentage injected dose per gram (%ID/g) of tissue and averaged 0.076%ID/g PE and 0.083%ID/g DVT. Lesion-to-background ratios averaged 12.8 (PE-to-lung), 7.2 (DVT-to-blood), and 117.0(DVT-to-muscle).

^99mTc-chSZ21F(ab)₂ with its modest affinity and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.

No relevant conflicts of interest to declare.