Biological Evaluation of 99mTc-Labeled Cyclic Glycoprotein IIb/IIIa Receptor Antagonists in the Canine Arteriovenous Shunt and Deep Vein Thrombosis Models: Effects of Chelators on Biologica

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• 作者：John A. Barrett ; David J. Damphousse ; Stuart J. Heminway ; Shuang Liu ; D. Scott Edwards ; Richard J. Looby ; and Timothy R. Carroll
• 刊名：Bioconjugate Chemistry
• 出版年：1996
• 出版时间：March 1996
• 年：1996
• 卷：7
• 期：2
• 页码：203 - 208
• 全文大小：325K
• 年卷期：v.7,no.2(March 1996)
• ISSN：1520-4812

文摘

A series of ^99mTc-labeled cyclic glycoprotein IIb/IIIareceptor antagonists,[^99mTcO(L1-III)]^-,[^99mTcO(L6-III)]^-,[^99mTcO(L1-V)]^-, and[^99mTcO(L6-V)]^-,were evaluated in a canine arteriovenous (AV)shunt model for their potential use as thrombus imaging agents.The thrombus formed consists of aplatelet-rich head and a fibrin-rich tail. All four agents wereincorporated into the growing thrombusunder both arterial (platelet-rich) and venous (platelet-poor)conditions. The rank order for uptakewas [^99mTcO(L1-V)]^-> [^99mTcO(L6-V)]^-> [^99mTcO(L6-III)]^-> [^99mTcO(L1-III)]^-(arterial range,5.8-0.47 % id/g; venous range, 0.58-0.04 % id/g). Theuptakes of both[^99mTcO(L6-III)]^-and [^99mTcO(L1-III)]^- under both arterial and venousconditions were not significantly greater than that of[^99mTc]albumin and [¹²⁵I]fibrinogen. In contrast, theuptakes of both[^99mTcO(L1-V)]^- and[^99mTcO(L6-V)]^-were significantly greater than those of[^99mTc]albumin and[¹²⁵I]fibrinogen and comparable to that of[¹¹¹In]platelets under both arterial and venousconditions. All four[^99mTc]chelator-peptideconjugatesare cleared faster than the controls with the clearance of theconjugates of peptide III faster thanthat of the conjugates of peptide V. The differences inincorporation are attributable to the effect ofboth the cyclic peptide and the chelator. The conjugate[^99mTcO(L1-V)]^- wasalso studied using acanine DVT (deep vein thrombosis) model.[^99mTcO(L1-V)]^-was actively incorporated into the growingthrombus 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 and10/1, respectively. This clearly demonstrated that the conjugate[^99mTcO(L1-V)]^- hasthe potentialfor rapid diagnosis of thrombolic events occurring under both arterialand venous conditions.