Occlusion of Animal Model Arteriovenous Malformations Using Vascular Targeting

This study assessed the efficacy of a pro-thrombotic VTA targeting phosphatidylserine (PS) in a radiation-primed AVM animal model. The model AVM was surgically created in rats by anastomosis of the left external jugular vein to the adjacent common carotid artery. After 6  weeks, the AVM was irradiated (20 Gy) using gamma knife surgery (GKS). A PS-targeting VTA was created by conjugation of annexin V with human thrombin and administered intravenously 3 weeks post-GKS or sham. Unconjugated thrombin was used as a non-targeting control. AVM thrombosis and occlusion w as monitored 3 weeks later by angiography and histology. Preliminary experiments established a safe dose of active thrombin for systemic administration. Subsequently, a single dose of annexin V–thrombin conjugate (0.77 mg/kg) resulted in angiographic AVM occlusion in sham (75%) and irradiated (6 3%) animals, while non-targeted thrombin did not. Lowering the conjugate dose (0.38 mg/kg) decreased angiographic AVM occlusion in sham (13%) relative to irradiated (80%) animals (p = 0.03) as did delivery of two consecutive doses of 0.38 mg/kg, 2 days apart (sham (0%); irradiated (78%);p = 0.003). These findings demonstrate efficacy of the PS-targeting VTA and the feasibility of a vascular targeting approach for occlusion of high-flow AVMs. Targeting specificity can be enhanced by radiation–sensitization and VTA dose modification.
Source: Translational Stroke Research - Category: Neurology Source Type: research