Occlusion of animal model arteriovenous malformations using vascular targeting

Andrew J. Gauden, Lucinda S. McRobb, Vivienne S. Lee, Sinduja Subramanian, Vaughan Moutrie, Zhenjun Zhao, Marcus A. Stoodley*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    Brain arteriovenous malformations (AVMs) are a significant cause of intracerebral hemorrhage in children and young adults. Currently, one third of patients have no viable treatment options. Vascular targeting agents (VTAs) are being designed to deliver pro-thrombotic molecules to the abnormal AVM vessels for rapid occlusion and cure. 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 was 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 (63%) 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.

    Original languageEnglish
    Pages (from-to)689-699
    Number of pages11
    JournalTranslational Stroke Research
    Issue number4
    Early online date5 Dec 2019
    Publication statusPublished - Aug 2020


    • Arteriovenous malformation
    • Endothelial cell
    • Phosphatidylserine
    • Radiosurgery
    • Thrombosis
    • Vascular targeting


    Dive into the research topics of 'Occlusion of animal model arteriovenous malformations using vascular targeting'. Together they form a unique fingerprint.

    Cite this