Abstract
Abstract 4387
A mouse/human chimeric monoclonal antibody F(ab)2 fragment, with high affinity for platelet glycoprotein IIIa was labelled with99mTc (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.
Author notes
Asterisk with author names denotes non-ASH members.
