Thrombus Imaging with a Technetium99m-Labeled, Activated Platelet Receptor-Binding Peptide (original) (raw)

The objective of this work was the preclinical evaluation of ""Tc-P280, a """Tc-labeled peptide having high affinity and specificity for the GPIIb/llla receptor expressed on activated platelets, for use as a thrombus imaging agent. Methods: The affinity and specificity of P280 peptide for the GPIIb/llla receptor was assessed by the inhibition of ADP-stimulated human platelet aggregation, the inhibi tion of the binding of fibrinogen to the GPIIb/llla receptor and the inhibition of the binding of vitronectin to the vitronectin receptor. P280 peptide was radiolabeled with 99mTcby ligand exchange using 99mTc-glucoheptonate. The ability of 99mTc-P280 to detect thrombi in vivo was assessed using a canine venous thrombosis model and the biodistribution of 99mTc-P280 was determined in rats and rabbits. Results: P280 peptide had an IC50 of 79 nM for the inhibition of aggregation of human platelets in platelet rich plasma, an ICgo of 6.8 nM for the inhibition of fibrinogen binding to the GPIIb/llla receptor and an ICso of 13 /nM for the inhibition of vitronectin binding to the vitronectin receptor, showing the high in vitro receptor binding affinity and specificity of the peptide. 99mTc-P280 was readily prepared in >90% radiochemical yield and purity and provided images of femoral vein thrombi in the canine model by 1 hr postinjection (thrombus-to-blood ratio of 4.4 and thrombus-tomuscle ratio of 11 at 4 hr). Dog, rat and rabbit studies all showed rapid clearance of the radiotracer from the blood and rapid renal excretion. Conclusion: The combination of high in vitro receptorbinding affinity and specificity, in vivo thrombus imaging and fast clearance support the evaluation of 99mTc-P280 as a clinical imag ing agent.