BIOLOGICAL EVALUATION OF TC-99M-LABELED CYCLIC GLYCOPROTEIN IIB IIIA RECEPTOR ANTAGONISTS IN THE CANINE ARTERIOVENOUS SHUNT AND DEEP-VEIN THROMBOSIS MODELS - EFFECTS OF CHELATORS ON BIOLOGICAL PROPERTIES OF [TC-99M]CHELATOR-PEPTIDE CONJUGATES/

A series of Tc-99m-labeled cyclic glycoprotein IIb/IIIa receptor antag onists, [(TcO)-Tc-99m(L1-III)](-), [(TcO)-Tc-99m(L6-III)](-), [(TcO)-T c-99m(L1-V)](-), and [(TcO)-Tc-99m(L6-V)](-), were evaluated in a cani ne arteriovenous (AV) shunt model for their potential use as thrombus imaging agents. The thrombus formed consists of a platelet-rich head a nd a fibrin-rich tail. All four agents were incorporated into the grow ing thrombus under both arterial (platelet-rich) and venous (platelet- poor) conditions. The rank order for uptake was [(TcO)-Tc-99m(L1-V)](- ) > [(TcO)-Tc-99m(L6-V)](-) > [(TcO)-Tc-99m(L6-III)](-) > [(TcO)-Tc-99 m(L1-III)](-) (arterial range, 5.8-0.47 % id/g; venous range, 0.58-0.0 4 % id/g). The uptakes of both [(TcO)-Tc-99m(L6-III)](-) and [(TcO)-Tc -99m(L1-III)](-) under both arterial and venous conditions were not si gnificantly greater than that of [Tc-99m]-albumin and [I-125]fibrinoge n In-contrast, the uptakes of both [(TcO)-Tc-99m(L1-V)](-) and [(TcO)- Tc-99m(L6-V)](-) were significantly greater than those of [Tc-99m]albu min and [I-125]fibrinogen and comparable to that of [In-111]platelets under both arterial and venous conditions. All four [Tc-99m]chelator-p eptide conjugates are cleared faster than the controls with the cleara nce of the conjugates of peptide III faster than that of the conjugate s of peptide V. The differences in incorporation are attributable to t he effect of both the cyclic peptide and the chelator. The conjugate [ (TcO)-Tc-99m(L1-V)](-) was also studied using a canine DVT (deep vein thrombosis) model. [(TcO)-Tc-99m(L1-V)](-) was actively incorporated i nto the growing thrombus with images clearly detectable within 15 min postinjection. At 2 h postinjection, thrombus/blood and thrombus/muscl e ratios [region of interest (ROI)/background] were approximately 7/1 and 10/1, respectively. This clearly demonstrated that the conjugate [ (TcO)-Tc-99m(L1-V)](-) has the potential for rapid diagnosis of thromb olic events occurring under both arterial and venous conditions.