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
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
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DOI：
10.1021/bc9500960
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发表时间：
1996-03-01
影响因子：
4.7
通讯作者：
Carroll, TR
中科院分区：
文献类型：
--
作者：
Barrett, JA;Damphousse, DJ;Carroll, TR
一系列tc -99m标记的环糖蛋白IIb/IIIa受体拮抗剂[(TcO)- tc -99m(L1-III)](-), [(TcO)- tc -99m(L6-III)](-), [(TcO)- tc -99m(L1-V)](-)，和[(TcO)- tc -99m(L6-V)](-)，在犬动静脉（AV）分流模型中评估其作为血栓显像剂的潜在用途。形成的血栓由富含血小板的头部和富含纤维蛋白的尾部组成。在动脉（血小板丰富）和静脉（血小板缺乏）条件下，所有四种药物都被纳入正在生长的血栓中。吸收的等级次序(TcO) tc - 99 m (L1-V )](-) > [( TcO) tc - 99 m (L6-V )](-) > [( TcO) tc - 99 m (L6-III )](-) > [( TcO) tc - 99 m (L1-III)](-)(动脉范围5.8 - -0.47% id / g;静脉范围0.58 - -0.04% id / g)。在动脉和静脉条件下，[(TcO)-Tc-99m(L6-III)]（-）和[(TcO)-Tc-99m(L1-III)]（-）的吸收量均不显著大于[Tc-99m]-白蛋白和[I-125]纤维蛋白原。相反，[(TcO)-Tc-99m(L1-V)]（-）和[(TcO)-Tc-99m(L6-V)]（-）的吸收量均显著大于[Tc-99m]白蛋白和[I-125]纤维蛋白原，与[In-111]血小板在动脉和静脉条件下的吸收量相当。所有四种[Tc-99m]螯合剂-肽偶联物的清除速度都比对照快，其中肽III偶联物的清除速度比肽v偶联物的清除速度快。掺入的差异归因于环肽和螯合剂的作用。结合物[(TcO)- tc -99m(L1-V)]（-）也用犬深静脉血栓形成模型进行了研究。[(TcO)- tc -99m(L1-V)]（-）主动融入生长中的血栓，注射后15分钟内图像清晰可见。注射后2小时，血栓/血液和血栓/肌肉比例[感兴趣区域(ROI)/背景]分别约为7/1和10/1。这清楚地表明，缀合物[(TcO)- tc -99m(L1-V)]（-）具有快速诊断动脉和静脉条件下发生的血栓事件的潜力。
A series of Tc-99m-labeled cyclic glycoprotein IIb/IIIa receptor antagonists, [(TcO)-Tc-99m(L1-III)](-), [(TcO)-Tc-99m(L6-III)](-), [(TcO)-Tc-99m(L1-V)](-), and [(TcO)-Tc-99m(L6-V)](-), were evaluated in a canine arteriovenous (AV) shunt model for their potential use as thrombus imaging agents. The thrombus formed consists of a platelet-rich head and a fibrin-rich tail. All four agents were incorporated into the growing 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-99m(L1-III)](-) (arterial range, 5.8-0.47 % id/g; venous range, 0.58-0.04 % 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 significantly greater than that of [Tc-99m]-albumin and [I-125]fibrinogen 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]albumin and [I-125]fibrinogen and comparable to that of [In-111]platelets under both arterial and venous conditions. All four [Tc-99m]chelator-peptide conjugates are cleared faster than the controls with the clearance of the conjugates of peptide III faster than that of the conjugates of peptide V. The differences in incorporation are attributable to the 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 into the growing thrombus with images clearly detectable within 15 min postinjection. At 2 h postinjection, thrombus/blood and thrombus/muscle 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 thrombolic events occurring under both arterial and venous conditions.